“The Brain for Not-So-Dummies”Osher Lifelong Learning Institute

NCSU

Eric W. Harris, PhD.

Follow up/News

1. Huntington’s Disease prevalence Worldwide `5-10 per 100,000 Varies regionally: e.g., higher in W. Eur. than Asia, very high near Lake Maricaibo Prevalence has risen, but could be due to detection, reporting, survival.

(Data from UK) Incidence seems stable (Spanish data)

Follow up/News

2. Finding a disease gene is useful: Cystic fibrosis gene found in 1989, And Kalydeco approved in 2012 for patients with certain mutations

Unfortunately not useful for patients with the most common mutation.

3. Great news about potential efficacy of drug Alzheimer’s Disease (AD) Significant benefit seen in only 1 of 2 measures Serious side-effect in subjects with ApoE-4 gene (~40% of AD cases) It targets amyloid – but accumulation of “tau” may be primary cause of dementia.

, but:

Interesting news…?

Week 4 - Treatment of Neurological (& Psychiatric) Disorders

Treatment Modalities

Surgery

Drugs

Electrical stimulation

Cognitive/behavioral

Biofeedback

Diet

Caveat – I am not a clinician

Pain Pain is the #1 reason for seeking medical treatment

Many types of pain (acute, chronic, visceral, migraine…)

Many causes (injury, inflammation, swelling, infection, neuropathy, MS, fibromyalgia…)

Gold-standard measurement: 10-point “Likert Scale”

Pain is a subjective experience, with many causes and heavily influenced by many things

Assessing pain is complicated, and dependent on contextInteresting studies looking in the brain (fMRI):

Different types of pain

Nociceptive pain: signals damage or potential damage (e.g., wound, cold…)

Neuropathic pain: results from disorders of the peripheral nervous system or the central nervous system.

Diabetic neuropathy is PNS neuropathic pain Post-stroke neuropathic pain is CNS neuropathic pain Many causes: radiation, injury, infection (e.g., post-herpetic neuralgia)…

Neuropathic pain may be associated with abnormal sensations (dysesthesia), pain from normally non-painful stimuli (allodynia). Common qualities include burning or coldness, "pins and needles", numbness and itching, aching.

Not synonymous with “neuropathy” (with means a nervous system dysfunction)

Neuropathic pain is a huge unmet medical need and market…

…But first a few words about drugs

Prescription drugs, unlike most things you can buy “over the counter”, go through a very rigorous approval process In the US, this is regulated by the FDA

BRIEF Overview of Drug Development Process

Drug approvals are based on evaluation of a lot of data

This is not the case for many medical treatments or claims (e.g., supplements, surgery, “alternative medicine”…)

Many things affect how well a drug will work for any given patient Weight & body type Genetics

Gender Genetics of “target tissue” AND of “off-target” tissue Liver and other metabolism (active metabolites?)

Diet Foods (e.g. grapefruit), supplements, other drugs

Disease status Dosing time of day Compliance …

A rare (unique?) ideal case

Drug Development - Comments

FDA-regulated drug development is a huge, demanding, but scientific process

Drug action is often not as a as simple “decreases this”, or “increases this”

No drug is perfectly “safe” in the whole human population

The drug approval process is based on trial population “benefit/risk”

Drugs for Pain Anesthetics

E.g., lidocaine, Novocain – block action potential propagation (via Na-channels)

Analgesics Opioids (activate “opiod receptors” that are activated by “endorphins”) NSAIDs (aspirin, ibuprofen, acetaminophen…) COX-2 inhibitors (most withdrawn due to cardiovascular concerns)

Drugs for neuropathic pain Steroids (reduce inflammation) Neurontin (gabapentin), Lyrica (pregabalin) – interesting discovery Antidepressnats and anticonvulsants often used for pain (e.g., carbamazepine for

trigeminal neuralgia) May be direct effect, may be effect on mood or sleep

Drugs for Pain – help from an unlikely source…

Cone snails – very, very interesting predators (?!)

(videos)

Their venom contains numerous substances designed to do one of three things “Taser” their prey “Narcotioze” their prey Paralyze their prey

One peptide in particular has found utility in the treatment of pain Ω-conopeptide MVIIa = ziconotide = Prialt; targets “N-type calcium channels” Must be administered intrathecally (into the CSF around the spinal cord) “For the management of severe chronic pain in patients for whom intrathecal therapy is

warranted, and who are intolerant of or refractory to other treatment…”

Other interesting treatments for pain

“Mirror Box” for phantom limb pain• Not universally effective• Perhaps most effective for “motor” pain (e.g., cramping)

Transcutaneous Electrical Nerve Stimulation (TENS)

Capsaicin patch Not the same 0.1%0.1%

Parkinson’s Disease (PD)

2nd most common neurodegenerative disease (after Alzheimer’s)

4 Cardinal Symptoms: Tremor - usually starts in limb or hand, rubbing of thumb & forefinger (pill-

rolling); tremor of hand at rest. Rigidity – stiffness, movement may become painful Bradykinesia – slowed movement, dragging of feet Postural instability – stooped, balance problem

Other common symptoms: Loss of automatic movements –less blinking, smiling, swinging arms when

walking, less gesturing when talking Speech changes - sofy, quick, slurred; hesitating before talking; monotone Writing changes - writing may be small (micrographia) and become difficult Loss of sense of smell

Parkinson’s Disease - pathologyLoss neurons in the Substantia Nigra (SN) that secrete dopamine (DA)

“Lewy Bodies”, made of the protein -synuclein

Brown is an -synuclein specific stain

SN is named for its dark pigmentation(due to neuromelanin in DA-releasing SN neurons)

Normal PD