Levodopa may improve vision in patients with macular degeneration

Date:
September 10, 2020
Source:
Elsevier
Summary:
Investigators have determined that treating patients with an
advanced form of age-related macular degeneration (AMD) with
levodopa, a safe and readily available drug commonly used to treat
Parkinson's disease, stabilized and improved their vision. It
reduced the number of treatments necessary to maintain vision,
and as such, will potentially reduce the burden of treating the
disease, financially and otherwise.



FULL STORY ========================================================================== Investigators have determined that treating patients with an advanced
form of age-related macular degeneration (AMD) with levodopa, a safe
and readily available drug commonly used to treat Parkinson's disease, stabilized and improved their vision. It reduced the number of treatments necessary to maintain vision, and as such, will potentially reduce the
burden of treating the disease, financially and otherwise. Their findings appear in the American Journal of Medicine, published by Elsevier.


==========================================================================
More than 15 percent of the US population over the age of 70 has AMD,
a common cause of blindness in developed nations. Neovascular AMD (nAMD)
is characterized by the abnormal growth of new blood vessels, triggered
by vascular endothelial growth factor (VEGF), which can cause fluid and
blood to leak in the subretinal space of the eye. While nAMD represents
only 10-15 percent of all AMD cases, it is responsible for 90 percent
of the vision loss attributed to the disease. The standard treatment
requires frequent injections of agents to block VEGF. While effective,
the injections are expensive and painful.

Earlier research found that patients being treated with levodopa for
movement disorders such as Parkinson's disease were significantly less
likely to develop any type of AMD. Lead investigator Robert W. Snyder,
MD, PhD, Department of Biomedical Engineering, The University of Arizona, Tucson, and Snyder Biomedical Corporation, Tucson, AZ, USA, explained, "Levodopa has a receptor (GPR143) selectively expressed on pigmented
cells. This receptor can be supportive of retinal health and survival,
which led to the development of our hypothesis that it may prevent or
treat AMD." The investigators developed two proof-of-concept studies to
test whether levodopa improves visual acuity and the anatomical changes
caused by nAMD. They also evaluated the safety and tolerability of the
drug in treating nAMD and whether treatment reduced or delayed the need
for anti-VEGF therapy.

In the first study, 20 patients newly diagnosed with nAMD who had never
had VEGF treatment were given a small daily dose of levodopa for one
month and were evaluated weekly by their referring retina specialist,
who determined whether anti-VEGF treatment was needed. In the second part
of the study, the patients who completed the first study and a second
group of 14 patients who had received anti-VEGF treatment for at least
three months before the study received escalating doses of levodopa to
test the tolerance and efficacy of the drug. The patients continued to
be evaluated monthly by their referring retina specialist.

This trial demonstrated for the first time that levodopa is safe, well- tolerated, and delayed anti-VEGF injection therapy while improving visual outcomes. In the first month, retinal fluid decreased by 29 percent. After
six months the decrease in retinal fluid was sustained and mean visual
acuity improved enabling patients in the first and second group to read
an additional line on the eye chart. This is the equivalent of improvement
from 20/40 to 20/ 32. Side effects were limited.

The investigators noted that levodopa may be unlikely as a standalone
treatment in patients with newly diagnosed nAMD since 11 of the patients
did require anti-VEGF injections. However, they required fewer than the standard monthly treatments, and in the second group, monthly injections
of anti-VEGF decreased by 52 percent.

According to Dr. Snyder, although this limited proof-of-concept study
included a small sample size and limited patient diversity, its findings suggest efficacy and support the targeting of the GPR13 receptor with
levodopa for the treatment of nAMD in future studies.

The concept had its genesis 20 years ago when Dr. Snyder began working
with co- investigator Brian S. McKay, who had developed techniques to
culture and examine retinal endothelial pigment cells. "We had a strong
desire to make an impact in AMD, and I had a strong hunch that Dr. McKay
could make a significant contribution," Dr. Snyder said. "Although this
is nowhere near completed, I am happy to say, 20 years later, we have
all persevered, and I believe the GPR143/ levodopa story will make a significant impact on our treatment and prevention of AMD."

========================================================================== Story Source: Materials provided by Elsevier. Note: Content may be edited
for style and length.


========================================================================== Journal Reference:
1. Anna G. Figueroa, Brennan M. Boyd, Cory A. Christensen, Cameron
G. Javid,
Brian S. McKay, Timothy C. Fagan, Robert W. Snyder. Levodopa
Positively Affects Neovascular Age-Related Macular
Degeneration. The American Journal of Medicine, 2020; DOI:
10.1016/j.amjmed.2020.05.038 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/09/200910120118.htm

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