Donald Harris

Donald Harris, well-known to the Brunswick Parkinson’s community for his quick wit and kindness, has died at age 81 after a brief acute illness.  Over the several years I knew Donald he always impressed me with his integrity, his sense of humor, and his ability to reduce complex discussions into clear choices; though often finishing a thought with an instruction to for me to “think about it.”  Usually the “it” would wind up being something unexpected and funny.  He could also be quite serious and thoughtful.  Donald had a keen mind and a good heart.  He will be missed by many.

Donald’s family is asking that memorial donations be made to the Maine Parkinson Society.   If you would like to do so, donate online by clicking the link here: https://www.maineparkinsonsociety.org/donate/  or, you may click to use the attached donation form by mail: Donation_Form

 

Update on marijuana in Parkinson disease

Medical marijuana has been a daily topic raised by Parkinson disease (PD) patients in my clinic for the last several years.   This is not surprising in a state with medical marijuana laws going back to 1998.  Often overlooked is the fact that under state law PD is not an indication for medical marijuana.  For those reasons in the winter 2016/2017 issue of MPDN the topic was discussed (1).   At the time I noted reliable scientific studies were limited, though the field, so to speak, was growing.   Although now 31 states and the District of Columbia have some form of medical marijuana law, it is still illegal at the federal level, and classified as a Schedule I substance.  The scheduling system is described by the Drug Enforcement Agency (DEA) as follows (2):

“Drugs, substances, and certain chemicals used to make drugs are classified into five (5) distinct categories or schedules depending upon the drug’s acceptable medical use and the drug’s abuse or dependency potential. The abuse rate is a determinate factor in the scheduling of the drug…”

The DEA goes on to say that

Schedule I drugs, substances, or chemicals are defined as drugs with no currently accepted medical use and a high potential for abuse. Some examples of Schedule I drugs are: heroin, lysergic acid diethylamide (LSD), marijuana (cannabis), 3,4-methylenedioxymethamphetamine (ecstasy), methaqualone, and peyote”.

Many in law and medicine have contested this Schedule I status for marijuana, though the discussion is far from over and the tide is moving forward.  Two countries: Uraguay and Canada have decriminalized marijuana, and many countries the world over are pursuing marijuana as a therapeutic, some of whom  such as Germany, have medical marijuana laws.  Research into medical applications of marijuana and its components is happening around the world, and PD is included among the potential therapeutic targets, though others are paving the way even faster.

In June of this year the Food and Drug Administration (FDA) approved a new drug to treat a severe form of seizures.

The drug Epidolex, is the first drug containing a purified form of a cannabidiol (CBD). 

CBD is a type of molecule in marijuana (footnote).  On the same date FDA Commissioner Scott Gottlieb, M.D. issued a statement on the importance of proper research to prove safe and effective medical uses for the components of marijuana (3).

He noted that over the prior decade the FDA had

“seen a growing interest in the development of therapies derived from marijuana and its components” for “a wide number of medical conditions.” 

Dr. Gottlieb reported that the FDA has been supportive of research in this area for many years, though marijuana is a Schedule I compound with known risks.  Therefore, he argued research with marijuana or its components should be held to the same standard as other drug compounds, especially in light of the fact that some proponents of medical marijuana use had called for a lower standard.

Nonetheless, “the FDA has an active program to assist drug developers who want to investigate marijuana or its components through properly controlled clinical trials, to demonstrate the potential for safe and effective uses.” 

To further development in this area the FDA has formed a Botanicals Team to provide scientific expertise on botanical issues for researchers developing drugs derived from plants, such as marijuana.

And, the FDA is not the only federal agency relaxing its stance on marijuana, or at least some components of the plant.  The DEA has rescheduled the epilepsy CBD drug Epidolex from Schedule I to Schedule V, which is the lowest degree of restriction:

“Schedule V drugs, substances, or chemicals are defined as drugs with lower potential for abuse than Schedule IV and consist of preparations containing limited quantities of certain narcotics. Schedule V drugs are generally used for antidiarrheal, antitussive, and analgesic purposes. Some examples of Schedule V drugs are: cough preparations with less than 200 milligrams of codeine or per 100 milliliters (Robitussin AC), Lomotil, Motofen, Lyrica, Parepectolin.”

This new scheduling likely opens the door to other cannabis-based medications. However, the DEA was clear that the rescheduling was only for this specific product.

Footnote: There are many different CBD molecules, see the article in reference 1.

REFERENCES

1.What about medical marijuana and PD? http://mainepdnews.org/2017/01/03/what-about-medical-marijuana-and-pd/

2. Drug Scheduling https://www.dea.gov/drug-scheduling

3. Statement by FDA Commissioner Scott Gottlieb, M.D., on the importance of conducting proper research to prove safe and effective medical uses for the active chemicals in marijuana and its components https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm611047.htm

Pipeline drugs, part 4: apomorphine

Apomorphine (Apokyn) is a dopamine delivered by multi-dose glass cartridges, 30 mg/3 mL with a multiple dose pen injector (APOKYN Pen).  Apokyn is FDA approved in the U.S. for the acute, intermittent treatment of hypomobility, OFF episodes, and unpredictable ON/OFF episodes associated with advanced Parkinson disease (PD).  It is used by a relatively small number of patients in the U.S.  However, different formulations of apomorphine are available outside the U.S., and different formulations are under investigation within our borders.

One study evaluated APL-130277, a sublingual (beneath the tongue) apomorphine oral strip, as an acute, effective, noninvasive treatment for OFF episodes (1).  This was a phase II, open-label, proof-of-concept study.

In open-label studies, patients know they are taking the study drug and there is no placebo, thus no blind.  Proof-of-concept studies are designed to verify that some concept has practical potential, such as using a sublingual version of the drug for a certain indication.  

In this study patients presented to clinic in the morning hours “in the practically defined OFF state” (before  taking their morning medications) and were given APL-130277 10 mg.  PD motor scores using MDS-UPDRS III were recorded before dosing and at 15, 30, 45, 60, and 90 minutes.  If a full ON state was not achieved within 3 hours, the dose was increased in 5 mg increments until the patient was either ON, or had taken 30 mg.  Of the 19 people with PD treated, 15 (78.9%) reached a full ON response within 30 minutes, and 6 of the 15 patients reached ON within 15 minutes.  Average duration of ON was 50 minutes, and nine patients remained fully ON for 90 or more minutes.  No patients discontinued the drug due to adverse event, though dizziness occurred in 36.8%, sleepiness in 31.6%, and nausea in 21.1%.

NCT0254269 is an open-label phase III study to examine long-term safety, tolerability, and efficacy of APL-1320277 in doses ranging from 10-35 mg for the treatment of OFF episodes in patients with PD (2).  Estimated enrollment will be 226 patients and recruitment is ongoing at many centers in the U.S. and Canada.

Apomorphine has also been developed as a drug which may be administered by pump.  Already available in some countries, it is currently in trials in the U.S.  The apomorphine pump is being tested as a method to avoid fluctuations in the motor symptoms of PD.  In a study published in 2017, authors noted that people with advanced PD and contraindications for deep brain stimulation (DBS) might benefit from apomorphine as an add-on to existing medications, and evaluated the motor and nonmotor symptoms in advanced PD (3).

A small cohort of 12 patients with advanced PD were assessed before and after 6 months of apomorphine with a type of brain imaging called 18F-fluorodeoxyglucose positron emission tomography (PET scan) and “exhaustive clinical assessments.”  Authors noted that after 6 months of therapy they were able to significantly reduce oral PD meds (and thus reduce risk of side effects from those meds), and that motor and nonmotor scores improved “with a beneficial effect on executive functions, quality of life and apathy.”  Brain PET scan of these patients reportedly revealed significant metabolic changes consistent with the improvements in clinical scores.  The authors noted, “these preliminary results have to be confirmed by further studies.”

NCT02339064 is a phase III, 52-week safety study being called INFUS-ON, which is an actively recruiting, multicenter, open-label trial to assess the long-term safety and tolerability of continuous subcutaneous infusion of apomorphine in advanced PD patients with unsatisfactory motor fluctuations while using levodopa and at least one other class of drugs or mode of therapy for PD (4).  The study will also evaluate reductions in OFF time and improvements in ON time without troublesome dyskinesias.

 

REFERENCES

  1. Hauser, et al. Sublingual apomorphine (APL-130277) for the acute conversion of OFF to ON in Parkinson’s disease. Mov Disord. 2016;31(9):1366-72.
  2. https://clinicaltrials.gov/ct2/show/NCT02542696?term=sublingual+apomorphine&cond=Parkinson+Disease&rank=36
  3. Auffret, et al, Apomorphine pump in advanced Parkinson’s disease: Effects on motor and nonmotor symptoms with brain metabolism correlations. J Neurol Sci. 2017;372:279-287.
  4. https://clinicaltrials.gov/ct2/show/NCT02339064?term=apomorphine+pump&cond=Parkinson+Disease&rank=6

FDA approval of inhaled levodopa delayed

In the spring, 2018 issue of MPDN, the drug INBRIJA was discussed (1).  INBRIJA is a self-administered, orally inhaled form of levodopa (similar to an asthma inhaler) which if approved by the Food and Drug Administration (FDA), will be indicated for symptoms of OFF periods in people who take carbidopa/levodopa for Parkinson’s disease.  In other words, it will serve as a rescue drug for OFF periods.  As noted in that article, in February Acorda Therapeutics, Inc. announced the FDA had accepted the New Drug Application (NDA) for INBRIJA.  Under the Prescription Drug User Fee Act (PDUFA), the FDA set a target date of October 5, 2018.   However, the FDA announced on September 13 that PDUFA date for the drug been extended to January 5, 2019.   This delay comes after Acorda provided more data in response to FDA requests for additional information on chemistry, manufacturing, and controls (CMC).   Per the Acorda website press release, “FDA determined that these submissions constitute a major amendment and will take additional time to review” (2).

  1. Pipeline drugs, part 1: levodopa  http://mainepdnews.org/2018/03/24/pipeline-drugs-part-1-levodopa/
  2. http://ir.acorda.com/investors/investor-news/investor-news-details/2018/Acorda-Announces-FDA-Extends-INBRIJA-NDA-Review-Period/default.aspx

Jennifer Bryce to offer speech and language care at Aroostook Medical Center

Jennifer H. Bryce, MA, CCC-SLP, (speech & language pathologist), certified in LSVT-LOUD, has moved from the Boothbay and Damariscotta area, where in addition to her professional role she started and led the Parkinson disease support group for several years.   A loss to one region is a gain for others in Maine however.  She has returned home to Aroostook County, where she is available to provide treatment to people with PD.   If interested, please let your health care provider know that referrals can be sent to:   The Aroostook Medical Center,  Fax: 207-768-4734,  Phone: 207-768-4735.