New Developments in Parkinson’s Disease Research

Parkinson's Disease

With Parkinson’s disease (PD) affecting the lives of millions of people, reliable and effective diagnostics and treatments are needed to ease the burden of disease on individuals and society as a whole. With knowledge of the disease growing each year, investment in research has accelerated, offering hope to people living with challenging PD symptoms.

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Over 25 drugs being developed in Autistic Disorder pipeline landscape

Autism Spectrum Disorder puzzle illustration

Autistic disorder, also known as Autism Spectrum Disorder (ASD), encompasses a spectrum of neurodevelopmental disabilities. Ultimately, research continues to reveal factors that correlate with ASD risk, but no causal determinations have been made. This leaves much room for discovery with investigators continuing to elucidate new variants conveying genetic risk, or new environmental correlates that require further study.

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A Phase 2/3 Clinical Trial of Trigriluzole for Alzheimer’s Disease

The first patient has been enrolled in a Phase 2/3 clinical trial of trigriluzole (BHV-4157), a novel glutamate modulator for the treatment of mild-to-moderate Alzheimer’s disease (AD). The trial is a randomized, double-blind, placebo-controlled trial evaluating the efficacy and safety of trigriluzole in patients diagnosed with AD of mild-to-moderate severity (Mini-Mental State Examination scores of 14-24 at screening), and is being conducted in collaboration with the Alzheimer’s Disease Cooperative Study (ADCS) at sites throughout the USA.Howard Feldman, MD, FRCP, Director of the ADCS and Professor of Neurosciences at University of California San Diego School of Medicine added, “The preclinical evidence for the active metabolite of trigriluzole to modulate glutamate and confer neuroprotective effects in patients with AD is compelling, and the new formulation of trigriluzole should improve its pharmaceutical properties with potential for efficacy in AD.”

Alzheimer’s disease is a progressive, fatal neurodegenerative dementia that accounts for 60 ? 80 percent of dementia cases. Alzheimer’s disease currently has no cure. Although there are FDA-approved medications for symptomatic treatment of AD, their clinical benefits are generally limited. Novel therapeutic approaches aimed at normalizing synaptic and extra-synaptic glutamate levels, such as trigriluzole, may offer the potential for symptomatic benefit in AD by improving cognitive function, as well as the potential for disease modification by preventing the loss of synapses.

The Phase 2/3 clinical trial (clinicaltrials.gov identifier NCT03605667) is a randomized, double-blind, placebo-controlled trial evaluating the efficacy and safety of trigriluzole in patients diagnosed with AD of mild-to-moderate severity (Mini-Mental State Examination scores of 14-24 at screening). Patients who have been taking stable doses of FDA-approved AD medications (AchEI also known as acetylcholinesterase inhibitors and/or memantine) for a minimum of three months prior to screening and who are willing to remain on the same regimen for the duration of the trial may be eligible to participate. Approximately 292 patients will be randomized on a 1:1 basis to receive 280 mg of trigriluzole or placebo, taken orally at bedtime. Duration of treatment will be 48 weeks.

About Trigriluzole
Trigriluzole is a third-generation prodrug and new chemical entity that modulates glutamate, the most abundant excitatory neurotransmitter in the human body. Trigriluzole has a wide range of pharmacological actions, including interactions with several types of ion channels, cellular signaling mechanisms and facilitation of glutamate reuptake. Some potential targets related to trigriluzole’s mechanism of action include (1) reducing presynaptic glutamate release through actions at the voltage-gated ion channels, (2) facilitating glutamate uptake via EAATs located on glial cells, (3) enhancing transmission through synaptic AMPA receptors, (4) altering GABAergic neurotransmission, and (5) effecting neurotrophic agents such as BDNF. Several of these targets of trigriluzole balance abnormalities observed in human AD post-mortem tissue as well as in AD animal models. As such, trigriluzole potentially offers neuroprotective effects at the level of the synapse as well as improved synaptic functioning, mechanisms that could exert both symptomatic and disease-modifying effects in AD.

Displayed with permission of PR Newswire; Image courtesy of geralt at Pixabay (Free Lic CC0)

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Finding New Treatments for Breast Cancer with Brain Metastases

As if Breast Cancer or Brain Cancer alone were not enough to combat — patients with both now?have new hope in light of fledgling research that is showing progress.

Once breast cancer metastasizes into other areas of the body, particularly the brain, it becomes much more dangerous. And while the National Cancer Institute spends more than $500 million dollars per year on breast cancer research, only two to five percent of this funding goes to study how the disease spreads.

A clinical trial is open nationwide through the Academic Breast Cancer Consortium (ABRCC), giving access to an exciting novel drug therapy combination. The tucatinib, palbocilib and letrozole trial is coordinated by ABRCC and currently open for enrollment at the University of Colorado Cancer Center; University of Texas Health and Science Center in San Antonio, TX; Stony Brook University, NY; University of Arizona, Tucson, AZ; and University of New Mexico, Albuquerque, NM and will also be accruing patients at Northwestern University, Chicago, IL.

There are three well-established predictive markers of breast cancer. They are estrogen receptors (ER), progesterone receptors (PR), and the growth factor receptor HER2, these receptors may be blocked with targeted drugs to stop cancer growth. Breast cancers lacking these three markers are referred to as ?triple-negative? but clinicians and scientists are quickly learning more about cancers that have all three receptors, which are often called ?triple-positive.? There are treatments against each target individually, but when multiple drivers are present, as in ?triple-positive? breast cancer, blocking one often results in cancer nimbly switching to driving its growth with the other two.

The study combines tucatinib, which inhibits HER2, with letrozole targeting ER and PR hormone receptors, and the drug palbociclib, which targets CDK proteins that help cancer cells rush through the process of replication. The three had not been tried together until Elena Shagisultanova, MD, PhD, a breast cancer specialist at UCH, hypothesized there could be a way to target all three drivers at the same time with better results than targeting combinations of any two.

?When metastatic cancer spreads to the brain, it can be especially challenging,? says Dr Peter Kabos, the National Medical Director of the Academic Breast Cancer Consortium (ABRCC) and the Kabos Research Lab for Breast Cancer at UC Denver. ?Many medications aren?t effective in the brain, but exciting early clinical trial data for tucatinib shows that it may be one of the drugs that can penetrate the blood-brain barrier to combat brain metastases.

The trial is funded by the Pfizer ASPIRE Award in Breast Cancer Research. Cascadian Therapeutics and Pfizer are providing the study drugs tucatinib and palbociclib. For more information about trial eligibility and participation, contact brad.mackay@ucdenver.edu or emily.berens@ucdenver.edu

Article excerpted with permission from the University of Colorado Cancer Center blog — for the complete story, click here.