Targeting B Cells May Help With MS

PHILADELPHIA—A new study suggests that targeting B cells may be associated with reduced disease activity for people with multiple sclerosis (MS). The study was presented at the 66th Annual Meeting of the American Academy of Neurology.

A total of 231 people with relapsing-remitting MS received either a placebo or one of several low dosages of ofatumumab, an anti-B cell antibody, for 24 weeks, the first 12 of which were the placebo-controlled period.

The main objective was to determine the effects of ofatumumab dosing regimens, compared with placebo, on the total number of new brain lesions assessed every four weeks during a 12-week period.

All dose groups, including placebo, showed lesion activity in the first four weeks. Lesion suppression occurred in all ofatumumab dose groups from weeks four to 12. Researchers measured the amount of B cells in participants and compared it with the total number of new brain lesions that appeared on brain scans, which is a marker of disease activity.

When B cells were reduced to below a threshold of 64 cells/µL, disease activity, as measured by appearance of new brain lesions, was significantly reduced. On average, participants had an annualized rate of less than one new brain lesion per year when B cells were maintained below a threshold of 32 to 64 cells/µL, compared with 16 lesions without treatment.

The most common side effects, defined as those occurring in at least 5% of participants and at a rate twice that of placebo for weeks zero to 12, were injection-related reaction, dizziness, anxiety, fever, respiratory tract infection, and nerve pain.

Study author Daren Austin, PhD, of GlaxoSmithKline in Uxbridge, United Kingdom, said that the study results also suggest that peripheral, rather than central, B cells may be the most relevant target for anti-B cell therapy.

“These results need to be validated, of course, but the findings are interesting,” Dr. Austin said. “They provide new insight into the mechanism of B cells in MS and present a possible new target threshold for exploring the potential benefit of anti-B cell therapy.”

Ofatumumab is not approved anywhere in the world for use in the treatment of MS.

NR Narrowing of Carotid Artery Without Warning May Signal Memory and Cognitive Decline
Narrowing of the carotid artery without any symptoms may be linked to problems in learning, memory, thinking, and decision-making, compared with people with similar risk factors but no narrowing of the carotid artery, according to a study presented by Moira Dux, PhD.

“To date, the focus of diagnosis and management of carotid artery blockages has been prevention of stroke, since that was the only harm that these blockages were thought to cause to patients,” said principal investigator Brajesh K. Lal, MD, of the VA Maryland Health Care System’s Baltimore VA Medical Center and the University of Maryland School of Medicine in Baltimore. “These results underscore the importance of assessing the status of memory and thinking in people with carotid artery narrowing.”

The study involved 67 people with asymptomatic carotid stenosis (ACS) and a 50% reduction in the diameter of the artery and 60 people with vascular risk factors but without the condition. Risk factors included diabetes, high blood pressure, high blood cholesterol, and coronary artery disease. The participants underwent extensive testing for overall thinking abilities and for specific aspects of thinking, such as processing speed, learning, memory, decision-making, and language.

Patients with ACS performed significantly worse on the overall memory and thinking tests. On testing of specific aspects of thinking, they performed worse on tests for motor and processing speed and tests for learning and memory. Language scores did not differ between the two groups.

“If these findings are confirmed in larger studies, they [will] hold significant implications for new treatment targets and open the door for more questions such as: should these patients be treated more aggressively with medications, cognitive rehabilitation, or even surgery to open up the artery,” said Dr. Lal. “I anticipate a large number of follow-up studies searching for causes and the best treatment option for this newly identified morbidity associated with carotid narrowing.”

Study Examines Risk of Early Death for People With Mild Cognitive Impairment
One of the first studies to look at a relationship between death and the two types of mild cognitive impairment (MCI) suggests that people who have cognitive problems but no memory problems might have a higher death rate in a period of six years, compared with people who have no cognitive or memory problems. The same increased death rate was suggested in the study for individuals who have MCI with memory decline. Patients with MCI and no memory loss had the highest death rate, however.

“Currently, there is little information about death and the types of memory loss that affect many millions of Americans,” said study author Maria Vassilaki, MD, of the Mayo Clinic in Rochester, Minnesota. “Exploring how memory may or may not be linked with the length of life a person has is of tremendous significance as the population ages.” For the study, 862 people with thinking problems and 1,292 with no thinking problems between the ages of 70 and 89 were followed for nearly six years. Participants were from Olmsted County, Minnesota, and were given tests at the start of the study and every 15 months to assess their thinking abilities.

After six years, 331 of the group with MCI and 224 of the group without MCI died. Those who had MCI had an 80% higher death rate during the study than those without MCI. People with MCI and no memory loss had more than twice the death rate during the study than those without MCI, while people with MCI with memory loss had a 68% higher death rate during the study than those without MCI.

Low Tolerance for Pain? The Reason May Be Genetic
Researchers may have identified genes that affect individuals’ tolerance for pain. “Our study is quite significant because it provides an objective way to understand pain and why different individuals have different pain tolerance levels,” said study author Tobore Onojjighofia, MD, MPH, who is affiliated with Proove Biosciences. “Identifying whether a person has these four genes could help doctors better understand a patient’s perception of pain.”

Researchers evaluated 2,721 people diagnosed with chronic pain for the genes COMT, DRD2, DRD1, and OPRK1. Participants, all of whom were taking prescription opioid pain medications, were asked to rate their perception of pain on a scale from 0 to 10. People who rated their pain as 0 were excluded from further study. Low pain perception was defined as a score of 1, 2, or 3; moderate pain perception as a score of 4, 5, or 6; and high pain perception as a score of 7 or higher. Approximately 9% of the participants had low pain perception, 46% had moderate pain perception, and 45% had high pain perception. The researchers found that the DRD1 gene variant was 33% more prevalent in the low pain group than in the high pain group. Among people with a moderate pain perception, the COMT and OPRK variants were found 25% and 19% more often, respectively, than in individuals with a high pain perception. The DRD2 variant was 25% more common among people with a high pain perception, compared with people with moderate pain.

“Chronic pain can affect every other part of life,” said Dr. Onojjighofia. “Finding genes that may play a role in pain perception could provide a target for developing new therapies.

PHILADELPHIA—A new study suggests that targeting B cells may be associated with reduced disease activity for people with multiple sclerosis (MS). The study was presented at the 66th Annual Meeting of the American Academy of Neurology.

A total of 231 people with relapsing-remitting MS received either a placebo or one of several low dosages of ofatumumab, an anti-B cell antibody, for 24 weeks, the first 12 of which were the placebo-controlled period.

The main objective was to determine the effects of ofatumumab dosing regimens, compared with placebo, on the total number of new brain lesions assessed every four weeks during a 12-week period.

All dose groups, including placebo, showed lesion activity in the first four weeks. Lesion suppression occurred in all ofatumumab dose groups from weeks four to 12. Researchers measured the amount of B cells in participants and compared it with the total number of new brain lesions that appeared on brain scans, which is a marker of disease activity.

When B cells were reduced to below a threshold of 64 cells/µL, disease activity, as measured by appearance of new brain lesions, was significantly reduced. On average, participants had an annualized rate of less than one new brain lesion per year when B cells were maintained below a threshold of 32 to 64 cells/µL, compared with 16 lesions without treatment.

The most common side effects, defined as those occurring in at least 5% of participants and at a rate twice that of placebo for weeks zero to 12, were injection-related reaction, dizziness, anxiety, fever, respiratory tract infection, and nerve pain.

Study author Daren Austin, PhD, of GlaxoSmithKline in Uxbridge, United Kingdom, said that the study results also suggest that peripheral, rather than central, B cells may be the most relevant target for anti-B cell therapy.

“These results need to be validated, of course, but the findings are interesting,” Dr. Austin said. “They provide new insight into the mechanism of B cells in MS and present a possible new target threshold for exploring the potential benefit of anti-B cell therapy.”

Ofatumumab is not approved anywhere in the world for use in the treatment of MS.

NR Narrowing of Carotid Artery Without Warning May Signal Memory and Cognitive Decline
Narrowing of the carotid artery without any symptoms may be linked to problems in learning, memory, thinking, and decision-making, compared with people with similar risk factors but no narrowing of the carotid artery, according to a study presented by Moira Dux, PhD.

“To date, the focus of diagnosis and management of carotid artery blockages has been prevention of stroke, since that was the only harm that these blockages were thought to cause to patients,” said principal investigator Brajesh K. Lal, MD, of the VA Maryland Health Care System’s Baltimore VA Medical Center and the University of Maryland School of Medicine in Baltimore. “These results underscore the importance of assessing the status of memory and thinking in people with carotid artery narrowing.”

The study involved 67 people with asymptomatic carotid stenosis (ACS) and a 50% reduction in the diameter of the artery and 60 people with vascular risk factors but without the condition. Risk factors included diabetes, high blood pressure, high blood cholesterol, and coronary artery disease. The participants underwent extensive testing for overall thinking abilities and for specific aspects of thinking, such as processing speed, learning, memory, decision-making, and language.

Patients with ACS performed significantly worse on the overall memory and thinking tests. On testing of specific aspects of thinking, they performed worse on tests for motor and processing speed and tests for learning and memory. Language scores did not differ between the two groups.

“If these findings are confirmed in larger studies, they [will] hold significant implications for new treatment targets and open the door for more questions such as: should these patients be treated more aggressively with medications, cognitive rehabilitation, or even surgery to open up the artery,” said Dr. Lal. “I anticipate a large number of follow-up studies searching for causes and the best treatment option for this newly identified morbidity associated with carotid narrowing.”

Study Examines Risk of Early Death for People With Mild Cognitive Impairment
One of the first studies to look at a relationship between death and the two types of mild cognitive impairment (MCI) suggests that people who have cognitive problems but no memory problems might have a higher death rate in a period of six years, compared with people who have no cognitive or memory problems. The same increased death rate was suggested in the study for individuals who have MCI with memory decline. Patients with MCI and no memory loss had the highest death rate, however.

“Currently, there is little information about death and the types of memory loss that affect many millions of Americans,” said study author Maria Vassilaki, MD, of the Mayo Clinic in Rochester, Minnesota. “Exploring how memory may or may not be linked with the length of life a person has is of tremendous significance as the population ages.” For the study, 862 people with thinking problems and 1,292 with no thinking problems between the ages of 70 and 89 were followed for nearly six years. Participants were from Olmsted County, Minnesota, and were given tests at the start of the study and every 15 months to assess their thinking abilities.

After six years, 331 of the group with MCI and 224 of the group without MCI died. Those who had MCI had an 80% higher death rate during the study than those without MCI. People with MCI and no memory loss had more than twice the death rate during the study than those without MCI, while people with MCI with memory loss had a 68% higher death rate during the study than those without MCI.

Low Tolerance for Pain? The Reason May Be Genetic
Researchers may have identified genes that affect individuals’ tolerance for pain. “Our study is quite significant because it provides an objective way to understand pain and why different individuals have different pain tolerance levels,” said study author Tobore Onojjighofia, MD, MPH, who is affiliated with Proove Biosciences. “Identifying whether a person has these four genes could help doctors better understand a patient’s perception of pain.”

Researchers evaluated 2,721 people diagnosed with chronic pain for the genes COMT, DRD2, DRD1, and OPRK1. Participants, all of whom were taking prescription opioid pain medications, were asked to rate their perception of pain on a scale from 0 to 10. People who rated their pain as 0 were excluded from further study. Low pain perception was defined as a score of 1, 2, or 3; moderate pain perception as a score of 4, 5, or 6; and high pain perception as a score of 7 or higher. Approximately 9% of the participants had low pain perception, 46% had moderate pain perception, and 45% had high pain perception. The researchers found that the DRD1 gene variant was 33% more prevalent in the low pain group than in the high pain group. Among people with a moderate pain perception, the COMT and OPRK variants were found 25% and 19% more often, respectively, than in individuals with a high pain perception. The DRD2 variant was 25% more common among people with a high pain perception, compared with people with moderate pain.

“Chronic pain can affect every other part of life,” said Dr. Onojjighofia. “Finding genes that may play a role in pain perception could provide a target for developing new therapies.

PHILADELPHIA—A new study suggests that targeting B cells may be associated with reduced disease activity for people with multiple sclerosis (MS). The study was presented at the 66th Annual Meeting of the American Academy of Neurology.

A total of 231 people with relapsing-remitting MS received either a placebo or one of several low dosages of ofatumumab, an anti-B cell antibody, for 24 weeks, the first 12 of which were the placebo-controlled period.

The main objective was to determine the effects of ofatumumab dosing regimens, compared with placebo, on the total number of new brain lesions assessed every four weeks during a 12-week period.

All dose groups, including placebo, showed lesion activity in the first four weeks. Lesion suppression occurred in all ofatumumab dose groups from weeks four to 12. Researchers measured the amount of B cells in participants and compared it with the total number of new brain lesions that appeared on brain scans, which is a marker of disease activity.

When B cells were reduced to below a threshold of 64 cells/µL, disease activity, as measured by appearance of new brain lesions, was significantly reduced. On average, participants had an annualized rate of less than one new brain lesion per year when B cells were maintained below a threshold of 32 to 64 cells/µL, compared with 16 lesions without treatment.

The most common side effects, defined as those occurring in at least 5% of participants and at a rate twice that of placebo for weeks zero to 12, were injection-related reaction, dizziness, anxiety, fever, respiratory tract infection, and nerve pain.

Study author Daren Austin, PhD, of GlaxoSmithKline in Uxbridge, United Kingdom, said that the study results also suggest that peripheral, rather than central, B cells may be the most relevant target for anti-B cell therapy.

“These results need to be validated, of course, but the findings are interesting,” Dr. Austin said. “They provide new insight into the mechanism of B cells in MS and present a possible new target threshold for exploring the potential benefit of anti-B cell therapy.”

Ofatumumab is not approved anywhere in the world for use in the treatment of MS.

NR Narrowing of Carotid Artery Without Warning May Signal Memory and Cognitive Decline
Narrowing of the carotid artery without any symptoms may be linked to problems in learning, memory, thinking, and decision-making, compared with people with similar risk factors but no narrowing of the carotid artery, according to a study presented by Moira Dux, PhD.

“To date, the focus of diagnosis and management of carotid artery blockages has been prevention of stroke, since that was the only harm that these blockages were thought to cause to patients,” said principal investigator Brajesh K. Lal, MD, of the VA Maryland Health Care System’s Baltimore VA Medical Center and the University of Maryland School of Medicine in Baltimore. “These results underscore the importance of assessing the status of memory and thinking in people with carotid artery narrowing.”

The study involved 67 people with asymptomatic carotid stenosis (ACS) and a 50% reduction in the diameter of the artery and 60 people with vascular risk factors but without the condition. Risk factors included diabetes, high blood pressure, high blood cholesterol, and coronary artery disease. The participants underwent extensive testing for overall thinking abilities and for specific aspects of thinking, such as processing speed, learning, memory, decision-making, and language.

Patients with ACS performed significantly worse on the overall memory and thinking tests. On testing of specific aspects of thinking, they performed worse on tests for motor and processing speed and tests for learning and memory. Language scores did not differ between the two groups.

“If these findings are confirmed in larger studies, they [will] hold significant implications for new treatment targets and open the door for more questions such as: should these patients be treated more aggressively with medications, cognitive rehabilitation, or even surgery to open up the artery,” said Dr. Lal. “I anticipate a large number of follow-up studies searching for causes and the best treatment option for this newly identified morbidity associated with carotid narrowing.”

Study Examines Risk of Early Death for People With Mild Cognitive Impairment
One of the first studies to look at a relationship between death and the two types of mild cognitive impairment (MCI) suggests that people who have cognitive problems but no memory problems might have a higher death rate in a period of six years, compared with people who have no cognitive or memory problems. The same increased death rate was suggested in the study for individuals who have MCI with memory decline. Patients with MCI and no memory loss had the highest death rate, however.

“Currently, there is little information about death and the types of memory loss that affect many millions of Americans,” said study author Maria Vassilaki, MD, of the Mayo Clinic in Rochester, Minnesota. “Exploring how memory may or may not be linked with the length of life a person has is of tremendous significance as the population ages.” For the study, 862 people with thinking problems and 1,292 with no thinking problems between the ages of 70 and 89 were followed for nearly six years. Participants were from Olmsted County, Minnesota, and were given tests at the start of the study and every 15 months to assess their thinking abilities.

After six years, 331 of the group with MCI and 224 of the group without MCI died. Those who had MCI had an 80% higher death rate during the study than those without MCI. People with MCI and no memory loss had more than twice the death rate during the study than those without MCI, while people with MCI with memory loss had a 68% higher death rate during the study than those without MCI.

Low Tolerance for Pain? The Reason May Be Genetic
Researchers may have identified genes that affect individuals’ tolerance for pain. “Our study is quite significant because it provides an objective way to understand pain and why different individuals have different pain tolerance levels,” said study author Tobore Onojjighofia, MD, MPH, who is affiliated with Proove Biosciences. “Identifying whether a person has these four genes could help doctors better understand a patient’s perception of pain.”

Researchers evaluated 2,721 people diagnosed with chronic pain for the genes COMT, DRD2, DRD1, and OPRK1. Participants, all of whom were taking prescription opioid pain medications, were asked to rate their perception of pain on a scale from 0 to 10. People who rated their pain as 0 were excluded from further study. Low pain perception was defined as a score of 1, 2, or 3; moderate pain perception as a score of 4, 5, or 6; and high pain perception as a score of 7 or higher. Approximately 9% of the participants had low pain perception, 46% had moderate pain perception, and 45% had high pain perception. The researchers found that the DRD1 gene variant was 33% more prevalent in the low pain group than in the high pain group. Among people with a moderate pain perception, the COMT and OPRK variants were found 25% and 19% more often, respectively, than in individuals with a high pain perception. The DRD2 variant was 25% more common among people with a high pain perception, compared with people with moderate pain.

“Chronic pain can affect every other part of life,” said Dr. Onojjighofia. “Finding genes that may play a role in pain perception could provide a target for developing new therapies.