Research suggests that a drug used to treat diabetes could be repurposed for early-stage Parkinson’s.
- In a study of people with
early-stage Parkinson’s disease, a GLP-1 receptor agonist showed promising
results in reducing impaired motor skills associated with Parkinson’s.
- Lixisenatid — commonly used
to treat diabetes — was given to half of the cohort for a year, and their
motor skills deterioration showed almost no progression compared with the
people who received a placebo.
- Experts say the results of
the study are promising but warrant further long-term research with larger
groups.
Scientists have found that a drug commonly used to treat type
2 diabetes can
help reduce the development of motor skills deterioration in people with
early-stage Parkinson’s,
according to the findings of a new study published in The New
England Journal of Medicine.
The study, which was randomized, double-blind, and
placebo-controlled, followed 156 participants in France whose diagnosis of
Parkinson’s had been within the last three years, were on a stable regime of
medication to treat symptoms, and who did not yet have marked decline in motor
skills. The participants were either given lixisenatide, a GLP-1
receptor agonist that is used to treat diabetes or a placebo.
After 12 months, the 78 people who had been given
lixisenatide showed virtually no further deterioration of motor skills that is
commonly seen with Parkinson’s disease, while those who were given a placebo
saw a worsening of those symptoms. Nearly half of the group who took
lixisenatide reported nausea and 13% experienced vomiting.
Robert
Gabbay, MD, PhD, chief scientific and medical officer at the American
Diabetes Association, told Medical News Today that while
GLP-1 receptors are a relatively new field, the results of the study were
promising.
“It is a fascinating study that is proof of concept that this
class of medications may have some protective effect and be of advantage to
someday treat Parkinson’s. It will be interesting to see if the results hold
true for other newer GLP-1 agents like Ozempic/Wegovy and Zepbound,” Gabbay
said.
How are Parkinson’s and diabetes connected?
Parkinson’s is a disorder characterized by significant
neurological decline that can manifest in tremors, motor
control problems, and dementia. There is no known cause, but it is associated
with a lack of dopamine in
the brain. It is the second most common neurological disease after
Alzheimer’s in the U.S., and it is believed that at least 500,000 adults in the
U.S. have it.
Daniel
Truong, MD, neurologist and medical director of the Truong Neuroscience
Institute at MemorialCare Orange Coast Medical Center in Fountain Valley, CA,
and editor-in-chief of the Journal of Clinical Parkinsonism and Related
Disorders, told MNT that links between Parkinson’s and diabetes hinge on
several common threads between the disorders:
- insulin
resistance and glucose dysregulation
- inflammation
and oxidative stress
- dysfunction
of mitochondria
- alpha-synuclein
pathology
- shared
genetic risk factors
“There is ongoing research exploring the potential links between diabetes
and Parkinson’s disease. Several studies have suggested that individuals with
diabetes may have a higher risk of developing Parkinson’s disease, and vice
versa,” Truong said.
“Chronic low-grade inflammation and
oxidative stress are common features of both diabetes and Parkinson’s disease.
Research suggests that inflammatory processes in the brain may play a role in
the progression of Parkinson’s disease, and there is evidence linking inflammation
to insulin resistance in diabetes.”
— Daniel Truong, MD
“Studies have shown that mitochondrial dysfunction
contributes to insulin resistance and beta-cell dysfunction in diabetes, while
mitochondrial impairment is also a key feature of dopaminergic neuron
degeneration in Parkinson’s disease,” Truong explained.
“Emerging evidence suggests that alpha-synuclein pathology
may also be present in peripheral tissues, including pancreatic beta cells in
individuals with diabetes. Further research could explore the role of
alpha-synuclein aggregation in diabetes-related complications and its potential
link to Parkinson’s disease,” he added.
Using a diabetes drug to treat Parkinson’s
GLP-1 (glucagon-like peptide-1) receptor agonists are part of
a treatment regimen for people with type 2 diabetes. They can help reproduce or
enhance the effects of a naturally occurring gut hormone that assists in the
control of blood
sugar levels, and they can also reduce appetite by working on brain hunger
centers; this is one of the reasons drugs like Ozempic and Wegovy have been
associated with weight loss.
Truong said that
a drug like lixisenatide has neuroprotective effects, which would clearly
provide some assistance for people with a neurological disorder like
Parkinson’s. But he also pointed out how common traits in both diabetes and
Parkinson’s can provide some insight into GLP-1 receptor agonists as a way to
reduce Parkinson’s symptoms.
“There is emerging evidence
suggesting shared pathophysiological mechanisms between diabetes and
Parkinson’s disease. For example, insulin resistance and impaired glucose
metabolism have been implicated in both conditions. Therefore, drugs that
target these mechanisms, such as GLP-1 RAs, might have beneficial effects in
both diseases.”— Daniel Truong, MD
“In some studies, the prevalence of Parkinson’s disease was
lower among patients with diabetes who were treated with glucagon-like
peptide-1 (GLP-1) receptor agonists or dipeptidyl peptidase-4 inhibitors, which
increase GLP-1 levels, than among patients who received other diabetes medications,”
Truong said.
Study limitations
Truong said that the study’s limitations warrant further
research to establish several aspects of long-term treatment of Parkinson’s
with GLP-1 receptor agonists: dose optimization, combination therapies, safety
and tolerability, and effects on the non-motor symptoms.
“Parkinson’s disease is associated with a wide range of
non-motor symptoms, including cognitive impairment, autonomic dysfunction,
and psychiatric symptoms. Future studies should investigate whether
lixisenatide has beneficial effects on non-motor symptoms in addition to motor
symptoms,” he said.
“Although the study suggested a potential neuroprotective
effect of lixisenatide, the underlying mechanisms are not fully understood.
Further research is needed to elucidate the specific neuroprotective mechanisms
of lixisenatide in Parkinson’s disease, including its effects on inflammation,
oxidative stress, mitochondrial function, and alpha-synuclein pathology,” he
explained.
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