February 26, 2016
OCTOBER 17, 2015 – An FDA-approved drug for leukemia
improved cognition, motor skills and non-motor function in patients with
Parkinson’s disease and Lewy body dementia in a small clinical trial, say
researchers at Georgetown University Medical Center (GUMC).
The drug, nilotinib (known as Tasigna® by Novartis) also led to
statistically significant and encouraging changes in toxic proteins linked to
disease progression.
The study’s findings were presented at Neuroscience 2015, the
annual meeting of the Society for Neuroscience, in Chicago on Oct. 17.
Charbel Moussa, MD, PhD, who directs Georgetown’s Laboratory of
Dementia and Parkinsonism, conducted the preclinical research that led to the
discovery of nilotinib for the treatment of neurodegenerative diseases.
WALKING AGAIN
To conduct the clinical study, he partnered with Fernando Pagan,
MD, a GUMC associate professor of neurology who directs the Movement Disorders
Program at MedStar Georgetown University Hospital.
“To my knowledge, this study represents the first time a therapy
appears to reverse – to a greater or lesser degree depending on stage of
disease – cognitive and motor decline in patients with these neurodegenerative
disorders,” says Pagan. “But it is critical to conduct larger and more
comprehensive studies before determining the drug’s true impact.”
The investigators report that one individual confined to a
wheelchair was able to walk again and that three others who could not speak
were able to hold conversations.
Pagan notes there was no control group for comparison in the
study, and that the drug was not compared with a placebo or other medications
used to treat Parkinson’s.
SAFETY TEST
But the researchers report that during use of the medication by
the participants, production of dopamine increased in many patients, requiring
doses of L-dopa and other dopamine-sparing drugs used to treat Parkinson’s to
be lowered or stopped.
Stopping nilotinib treatment appears to lead to cognitive and
motor decline despite reinstating L-dopa therapies.
The study’s primary objective was to test safety.
“The use of nilotinib in doses much smaller than are used to
treat cancer, which is up to 800 mg daily, was well tolerated with no serious
side effects,” Pagan explains. “The dose used in this study was 150 and 300 mg
daily.”
The researchers also found that the drug penetrates the
blood-brain barrier in amounts greater than dopamine drugs.
The observed efficacy in cognition, motor skills and non-motor
function improvement (such as constipation) for many patients was the most
dramatic result, Pagan notes.
“Study participants with earlier stage disease responded best,
as did those diagnosed with Lewy body dementia, often described as a
combination of Parkinson’s and Alzheimer’s diseases,” he says.
LIFE-CHANGING IMPROVEMENT
Alan Hoffman, a professor emeritus of social science education
at Georgia State University, was diagnosed with Parkinson’s disease in 1997. He
says he participated in several clinical trials with no benefit until he
enrolled in Pagan’s study.
“Before the nilotinib, I did almost nothing around the house,”
he says. “Now, I empty the garbage, unload the dishwasher, load the washer and
the dryer, set the table, even take responsibility for grilling.”
In the three weeks prior to enrolling in the study, Hoffman says
he fell eight times, but he only fell once during six months on the study. His
speech has improved, as has his thinking.
“My wife says it’s life-changing for her and for my children and
grandchildren,” Hoffman says. “To say that nilotinib has made a change in our
lives is a huge understatement.”
TRANSLATIONAL SUCCESS
Moussa, an inventor on a Georgetown University patent
application for nilotinib and other similar drugs for neurodegenerative
diseases, notes that the research went to clinical trials only two years after
his initial discovery.
He first set out to find approved cancer drugs that could
penetrate the blood-brain barrier and turn on the “garbage disposal machinery”
inside neurons to clear toxic intracellular proteins and prevent their
accumulation within, or secretion outside of, brain cells.
“A lot of institutions talk about expediting the translation of
research from the lab to the bedside, but it doesn’t happen quickly very
often,” Moussa says. “This is a solid example of how that is possible and
why it is so important.”
PATIENTS CONTINUE TREATMENT
Hoffman and other patients in the clinical trial can continue
taking nilotinib as part of an expanded access study. Georgetown
researchers are now planning larger clinical trials with nilotinib for patients
with Parkinson’s and other similar diseases including Alzheimer’s disease,
likely to begin in 2016.
The phase I study received philanthropic funding and was
supported by the Georgetown-Howard Universities Center for Clinical and
Translational Science.
Co-authors of the study represent the MedStar Georgetown
Movement Disorders Program, GUMC’s Translational Neurotherapeutics Program and
the Laboratory for Dementia and Parkinsonism, and the Georgetown-Howard
Universities Center for Clinical and Translational Science Clinical Research
Unit.
http://www.healthfeeds.co/2016/02/26/researchers-report-first-therapy-appearing-to-reverse-decline-in-parkinsons-drug-rehab-oregon/
No comments:
Post a Comment