Tag Archives: inflammation

Yes, Congress can accomplish something

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Here’s a great step forward: The Energy and Commerce Committee of the US House of Representatives has just approved the “National Plan to End Parkinson’s Act.”  Thanks in part to advocacy by CurePSP and other organizations devoted to the atypical Parkinsonisms, the bill includes not only PD but also PSP, multiple system atrophy, Lewy body dementia, corticobasal degeneration and Parkinson’s dementia. 

For the remaining required approvals, the bill will now proceed to the full House itself, then the Senate, then the President. (I recited that route for my international readers and for my US readers who doodled through civics class.)  Crucially, the bill was passed with full bipartisan support in the committee, which bodes well for its chances the rest of the way.

Here’s video of the committee’s session.

The bill directs the Department of Health and Human Services to create an advisory commission with representation from all relevant Federal agencies and some advocacy and research organizations as well as patients and caregivers.  Each year, the commission would assess the state of research and clinical care and formulate recommendation on how the various relevant Federal agencies could formulate and coordinate further research plans.  It would also interact with similar organizations internationally. A similar bill for Alzheimer’s disease was enacted in 2011 and has been working successfully by all accounts.

The commission would recommend spending levels for the Federal Government to advance these efforts, but the bill provides no funding for the work of the commission itself.  That would have to be absorbed by the existing budget of the Department of HHS.  (This is standard practice when Congress is interested in a specific medical cause.) 

The bill was first taken up by the committee in March, nine months ago.  One of its major advocates has been Congresswoman Jennifer Wexton of Virginia, who was diagnosed with PSP herself last summer and has been working with CurePSP and others to improve awareness of PSP nationally and to raise funding for research.  Here’s a press release from her office.   The lead sponsor of the bill is Congressman Gus Bilirakis of Florida, who has three close relatives with PD, but 167 other House members signed on as co-sponsors.  The Michael J. Fox Foundation has been working tirelessly for the bill.

I know you’ve been waiting for my editorial commentary.  Here it is:  This is great publicity for PSP, and it sure needs it. 

Congresswoman Wexton is the highest-profile celebrity with PSP since Dudley Moore, the British-American comic actor best known for the movies “10” and “Arthur,” announced his diagnosis of PSP in 1998.  His friends organized a star-studded benefit at Carnegie Hall in New York that raised $50,000 for CurePSP but he declined to become an activist in other ways.  (I was his neurologist, and he told me, “I’ll help out, but don’t want to be the poster child for PSP.”) Linda Ronstadt, the popular singer and Rock and Roll Hall of Fame member, announced in 2019 that her longstanding diagnosis of Parkinson’s had been changed to PSP.  She has not yet supported PSP-related activities of which I’m aware.  A few other less-famous celebrities with PSP have advanced awareness and fundraising, and we’re grateful to them and their families.  But when “progressive supranuclear palsy” is mentioned on the floor of the US House of Representatives and included in press releases, that’s rare and valuable publicity.

. . . and the hits keep on coming

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As promised, another installment of new research tidbits from Neuro 2023, held in London from October 19- 23, 2023 and co-sponsored by CurePSP and the PSP Association of the UK:

  • Now that inflammation has come under suspicion as an important part of the pathogenesis of PSP and other tauopathies, researchers have realized that many of the known or suspected risk factors for PSP include an inflammatory component.  These include bacterial infection, repetitive mild head injury, seizures, and autoimmune disease. (Karen Duff, University College London, UK)
  • The PROSPECT-M-UK study of the atypical Parkinsonisms, based in London but involving 29 centers throughout England and Wales, has been funded since 2015. This long-term observational study’s overall goal is to find diagnostic markers.  It has recruited 1,472 patients so far, of whom 661 have PSP.  Participants undergo neuro exams, receive brain imaging, and provide samples of blood, spinal fluid, and DNA.  (Riona Fumi, UCL, UK)
  • A form of tau protein known for 25 years is “high-molecular-weight tau.”  What makes it heavy is the inclusion of a couple of optional stretches of amino acids.  It turns out that this form of tau is more likely than ordinary tau to spread through the brain (called “seeding capacity”), and that the prevalence of HMW tau in various brain regions correlates well with the vulnerability of those regions to PSP. (Ivan Martinez-Valbuena, Rossy Institute, University of Toronto, Canada)
  • Previous comparisons of genetic variants between PSP and controls has revealed five genes that each contribute a bit to PSP risk.  Now, a sixth such gene, called C4A, has been discovered in the largest such study ever, including 2,779 patients with PSP and 5,584 controls.  C4A is involved in an important part of the immune system called the “complement cascade,” and is most active in the oligodendrocytes, one type of the brain’s glial cells. (Kurt Farrell, Mt. Sinai School of Medicine, New York, US)

More progress, more hope

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Sorry for the absence.  I was on vacation in the UK leading up the Neuro 2023 conference in London, co-sponsored by CurePSP and its British counterpart, the PSP Association.  Despite its generic name, the meeting was specifically on PSP and CBD.  But it did cover new developments in everything from DNA to lifestyle.  A few of the more interesting things I heard, and I’ll have another equally pithy batch for you soon:

  • There’s is good evidence that the protein misfolding starts in the intestine and migrates to the brain in Parkinson’s disease, but this seems not to be the case in PSP.  There’s little misfolded tau in the gut in PSP and it’s in a different form than misfolded tau in the brain. (Wendy Noble, University of Exeter, UK)
  • An infrastructure for a “rolling platform” trial is expected to be funded by the NIH as soon as a new federal budget is approved.  That’s where multiple medications are tested in parallel and all use the same placebo group.  This greatly reduces each participant’s chances of receiving a placebo.  It’s “rolling” because as one drug either succeeds or fails, another can replace it without disrupting the overall protocol. (Adam Boxer, UCSF, USA)
  • In PSP, inflammation is found in direct proportion to brain cell damage in the same areas.  This is further evidence that inflammation is an integral part of the pathogenesis of the disease. (Nigel Leigh, Brighton and Sussex Medical School, Brighton, UK)
  • Some drug companies contemplating PSP treatment trials are starting the process by studying the “patient journey” to determine how best to evaluate the effectiveness of their drugs. (Stephanie Oscarson, SJO Research and Consulting, Valley Forge, PA, USA)
  • A new way to measure drug trial outcome is “artificial intelligence-curated music therapy.”  That’s where a trial participant listens to various kinds and volumes of music with EEG electrodes in place on the scalp.  Then an AI algorithm selects the music that optimizes the frequencies and locations of brainwaves known to be associated with a feeling of wellbeing. (Colin Ewen, UCB (Pharma company), Slough, UK
  • Clinical trials expected to start in the next 6-12 months (Günter Höglinger, Ludwig Maximilian University, Munich, Germany)
    • Bepranemab: Anti-tau monoclonal antibody
    • FNP-233 (formerly ASN90): Promotes the attachment of N-acetylglucosamine to tau, reducing its likelihood of misfolding and aggregating.
    • AMX0035 (combination of taurursodiol and sodium phenylbutyrate): stabilizes mitochondrial membranes and improves protein quality-control
    • AZP2006: Improves recycling of progranulin by lysosomes, thereby reducing inflammation
    • GV1001: A fragment of the enzyme telomerase reverse transcriptase, mimicking its anti-inflammatory and other action

Appetizer, entrée and dessert

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. . . and today, three news morsels:

First, sleep: Researchers at UCSF led by Jun Yeop Oh sought correlations between loss of specific areas of brain cells in the autopsies of 12 people with Alzheimer’s and 10 with PSP who during life had had detailed sleep studies.  They found relationships between several specific abnormalities of sleep with loss of neurons in two clusters of cells in the hypothalamus that use orexin and histamine, respectively, as their neurotransmitters.  A third area known to be related to sleep, the (dopamine-using) locus ceruleus in the midbrain, showed little or no such correlation.  The authors conclude that this line of inquiry “is crucial in designing the next generation of sleep medications [by boosting orexin or histamine] and even slowing down the progress of neurodegenerative disease through early interventions.”

Next, tau: A report from Michela Marcatti and colleagues at University of Texas Medical Branch in Galveston describes important differences between Alzheimer’s and PSP in the way their abnormal tau acts on the brain’s synapses.  They specifically looked at soluble oligomers – clumps of only a few tau molecules that remain soluble in the brain’s fluids, making them far more toxic than the larger, insoluble neurofibrillary tangles.  They found that in AD, tau oligomers displace beta-amyloid oligomers from the synapses after the initial disease stages, which may explain why treatments aimed at beta-amyloid have failed to date.  This bolsters our hopes AD and PSP could share a common treatment. The authors also suggest that the various tau oligomers’ different patterns of attack on the synapses might explain the different subtypes of PSP. 

Finally, a new drug: The oral drug AZP2006 is presently in a clinical trial for PSP in Europe. It acts by enhancing the effect of progranulin, a protein involved in multiple cell processes with potential relationships to neurodegeneration.  Researchers at Alzprotect, the French drug company sponsoring the trial, published the effects of AZP2006 in cultures of rat brain cells (neurons and microglia together) and in mice that had been genetically engineered to age quickly. It reduced abnormal tau phosphorylation and inflammation in the cultures and slowed the rate of cognitive decline in the mice.  It actually restored some of the animals’ lost cognitive abilities (!!), but we don’t know how long that benefit would last or if it resulted from rescue of sick cells or from some more ordinary drug action.