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Nigel A. Calcutt

Nigel A. Calcutt is a researcher specializing in the study and treatment of peripheral nervous system disorders. His research primarily focuses on the mechanisms and therapeutics of diabetic peripheral neuropathy, including the use of muscarinic receptor antagonists to stimulate nerve repair and mitochondrial function. He has also co-authored studies evaluating diagnostic and physiological measures of neuropathy, such as rate-dependent depression of the Hoffmann reflex and nerve fiber density.

19 claims checked on air: 2 overstated 14 supported 3 unverified

What they said on air - supported

1 citing their own research

0:06:35supportedmoderateExciting Developments in the Treatment of Peripheral Neuropa

Around 30 million people in the United States suffer from some form of peripheral neuropathy.

"In the US, around 30 million people suffering from some form of peripheral neuropathy." (said at 0:06:35)

Epidemiological literature on the burden of peripheral neuropathy in the United States commonly estimates that 20 to 30 million Americans are affected by some form of peripheral neuropathy across various etiologies (including diabetic neuropathy, chemotherapy-induced neuropathy, toxic/metabolic causes, and idiopathic forms). Published reviews document that peripheral neuropathies affect over 20 million individuals in the US, making the speaker's figure of 'around 30 million' an accurate approximation of the broad epidemiological range.

0:06:45supportedhighExciting Developments in the Treatment of Peripheral Neuropa

Diabetes is the leading cause of peripheral neuropathy in the United States.

"So, the common causes of neuropathy in the US are No. 1 is diabetes." (said at 0:06:45)

Epidemiological literature and clinical reviews consistently identify diabetes mellitus as the leading cause of peripheral neuropathy in the United States and other Western nations, accounting for more than 50% of all diagnosed peripheral neuropathy cases.

0:08:40supportedmoderateExciting Developments in the Treatment of Peripheral Neuropa

Over the last 20 to 30 years in the United States, the rate of progression of diabetic neuropathy has slowed.

"We do know that over the last 20 to 30 years in the US the rate of the progression of neuropathy has been slowed." (said at 0:08:40)

Longitudinal cohort and national surveillance data in the United States demonstrate a secular decline in the progression and rate of diabetic neuropathy and its end-stage sequelae over the past several decades. Findings from the prospective Pittsburgh Epidemiology of Diabetes Complications Study revealed a significant decreasing trend in diabetic neuropathy across successive diagnosis cohorts evaluated at 20- and 25-year diabetes durations (P < 0.05). In addition, nationwide surveillance from 1990 to 2010 documented a 51.4% reduction in lower-extremity amputations among adults with diabetes, reflecting substantial deceleration in the severe progression of neuropathic and vascular disease.

0:12:12supportedhighExciting Developments in the Treatment of Peripheral Neuropa

For certain chemotherapeutic agents, 80% to 90% of patients are expected to develop peripheral neuropathy.

"Some of them it's 80 or 90% of patients would be expected to get neuropathy." (said at 0:12:12)

Clinical and epidemiological research confirms that for specific neurotoxic chemotherapeutic agents—notably platinum compounds such as oxaliplatin and certain taxanes—the overall incidence of chemotherapy-induced peripheral neuropathy (CIPN) can reach 80% to 90% or higher during active treatment. In large observational cohorts and systematic reviews evaluating neurotoxic regimens, acute or cumulative sensory neuropathy of any grade is documented in up to 90% or more of patients receiving these agents.

0:21:55supportedmoderateExciting Developments in the Treatment of Peripheral Neuropa

Pain affects approximately one-third to one-half of patients with diabetic neuropathy.

"the pain had always been there. It impacts about a third to a half of the patients with neuropathy." (said at 0:21:55)

Published epidemiological literature and systematic reviews confirm that painful diabetic peripheral neuropathy (PDPN) affects approximately one-third to one-half of individuals with diabetic peripheral neuropathy. A 2025 systematic review and meta-analysis of 41 observational studies found a pooled global prevalence of painful diabetic peripheral neuropathy of 46.7% (95% CI, 41.8–51.7%) among patients with diabetic neuropathy.

0:23:25supportedhighExciting Developments in the Treatment of Peripheral Neuropa

Pregabalin was approved by the FDA for the treatment of diabetic neuropathy pain.

"Pregabalin was approved, the son of gabapentin was approved for use in diabetic neuropathy, and suddenly there was a route that you could follow." (said at 0:23:25)

Pregabalin (Lyrica) received FDA approval specifically for the management of neuropathic pain associated with diabetic peripheral neuropathy (DPN), becoming one of the first oral medications approved for this indication and serving as a guideline-recommended first-line therapy.

0:23:45supportedhighExciting Developments in the Treatment of Peripheral Neuropa

There are no FDA-approved drugs in the United States to treat the underlying nerve degeneration and loss in diabetic neuropathy.

"Because nothing has ever been approved to treat diabetic neuropathy, the nerve degeneration and loss, there is no route." (said at 0:23:45)

The statement is accurate. While several medications (such as pregabalin, duloxetine, and tapentadol) are FDA-approved to manage symptoms and pain associated with diabetic peripheral neuropathy, there are currently no FDA-approved disease-modifying therapies aimed at slowing, stopping, or reversing the underlying nerve degeneration and structural loss.

0:26:46supportedlowExciting Developments in the Treatment of Peripheral Neuropa

Aldose reductase inhibitors effectively prevent cataractogenesis and treat complications of diabetes in rodent models.

"And aldose reductase inhibitors are perfect blockers of cataractogenesis. Um in fact, they cured most things in animals through the '60s and '70s and '80s. Um in all the animal models, they fixed pretty much everything." (said at 0:26:46)

Extensive preclinical literature from the 1960s through the 1980s and beyond demonstrates that aldose reductase inhibitors (ARIs, such as sorbinil) effectively block or reverse cataractogenesis and mitigate other diabetic complications (such as retinopathy, neuropathy, and nephropathy) in rodent and other animal models. In diabetic and galactosemic rodents, accumulation of sorbitol via the polyol pathway causes osmotic stress and tissue damage, which ARIs consistently prevented in laboratory models, despite subsequent challenges translating these robust animal results to human clinical trials.

0:27:20supportedmoderateExciting Developments in the Treatment of Peripheral Neuropa

In the lens of the eye, aldose reductase converts glucose to sorbitol, which acts as an osmolyte, causing lens fibers to swell and burst to form cataracts.

"basically the you know, very crudely the glucose gets into the cells of the lens. They swell because they make sorbitol. I mean, the progression of aldose reductase from glucose to fructose includes an intermediate sorbitol that is a very strong osmolyte. And so, the so sorbitol accumulates in the lens, they swell, the lens fibers burst and you and you start getting cataracts with these accumulations." (said at 0:27:20)

The speaker accurately describes the classic polyol pathway (osmotic) mechanism of diabetic cataractogenesis. Under hyperglycemic conditions, aldose reductase reduces excess intracellular glucose into sorbitol. Because sorbitol is poorly permeable to cell membranes, it accumulates intracellularly and acts as an osmolyte, drawing water into the lens fibers. This osmotic swelling leads to cellular disruption, membrane damage, and lens opacification (cataract formation). While additional factors such as oxidative stress and advanced glycation end-products also contribute in human diabetic cataracts, the aldose reductase-mediated sorbitol osmotic swelling mechanism is well established.

0:39:28supportedhighExciting Developments in the Treatment of Peripheral Neuropa

Pirenzepine does not cross into the central nervous system.

"pirenzepine was one of those drugs that existed that did not cross into the CNS. So, it made it purely a peripheral acting drug." (said at 0:39:28)

Pirenzepine is a selective M1 muscarinic receptor antagonist that is hydrophilic and does not effectively cross the blood-brain barrier under standard systemic administration, making its pharmacological actions predominantly restricted to the peripheral nervous system and peripheral tissues. It is widely used in pharmacological and clinical research specifically as a peripherally restricted muscarinic antagonist to distinguish central from peripheral cholinergic effects.

0:39:58supportedmoderateExciting Developments in the Treatment of Peripheral Neuropa

Pirenzepine was developed by Boehringer Ingelheim as an oral drug for gastric ulcers that blocks acetylcholine-driven release of hydrochloric acid in the stomach.

"pirenzepine existed and it had been used in millions of people around the world um for treating gastric ulcers. Um it was developed by a a German company, Boehringer Ingelheim. Um and you took it as an oral um pill, I believe. And it blocked acetylcholine um driven release of HCl in the stomach." (said at 0:39:58)

Pirenzepine is a selective muscarinic M1 receptor antagonist originally developed by Boehringer Ingelheim (marketed under brand names including Gastrozepin) as an oral therapeutic for peptic and gastric ulcers. Pharmacologically, it inhibits acetylcholine-mediated stimulation of gastric acid (hydrochloric acid) secretion by blocking muscarinic receptors involved in cholinergic signaling in the gastrointestinal tract.

0:42:07supportedhighExciting Developments in the Treatment of Peripheral Neuropa

High systemic doses of antimuscarinic medications commonly induce side effects such as dry mouth and tachycardia.

"When you have give too high doses systemically, you're going to start getting you know, the dry mouth, the tachycardias, the things that one associates with antimuscarinics in high doses." (said at 0:42:07)

The claim is supported by clinical literature. High systemic exposure or toxicity from antimuscarinic (parasympatholytic) agents classically produces peripheral anticholinergic manifestations, most notably dry mouth (xerostomia) and tachycardia.

0:42:28supportedhighExciting Developments in the Treatment of Peripheral Neuropa

Corneal confocal microscopy can be used to image sensory nerves live and in real time in humans or animals to measure nerve degeneration and regeneration.

"There's also a very interesting technique called corneal confocal microscopy which takes a confocal microscope and aims it at the eye... And it has been well documented now by a colleague of ours, um Rayaz Malik, who's worked on this now and really elevated it to an art form as well as a science form, that you can use these corneal confocal microscopes to look at nerves in real time... So, you can use this to measure degeneration, apply drugs to the eye and look at regeneration, all in a human or an animal live." (said at 0:42:28)

Corneal confocal microscopy (CCM) is an established, non-invasive in vivo imaging technique used in humans and animal models to visualize sub-basal corneal nerve fibers in real time. Extensive research, notably led by Rayaz Malik and colleagues, demonstrates that CCM detects small sensory nerve fiber degeneration in neuropathies (such as diabetic peripheral neuropathy) and captures early nerve regeneration following therapeutic or surgical interventions.

0:50:25supportedhighExciting Developments in the Treatment of Peripheral Neuropa

Standard nerve conduction studies assess large-fiber nerve function rather than small-fiber nerve function.

"the nerve conduction studies are large fiber studies and a lot of the a lot of the problems that we've described in diabetic neuropathy are small fiber." (said at 0:50:25)

Standard nerve conduction studies evaluate myelinated, large-diameter A-alpha and A-beta nerve fibers and cannot record the activity of unmyelinated (C) or thinly myelinated (A-delta) small fibers. Because early or painful diabetic peripheral neuropathy frequently presents as small-fiber pathology, nerve conduction studies are often normal in these patients and require specialized modalities (such as skin biopsy to assess intraepidermal nerve fiber density, corneal confocal microscopy, or quantitative sensory testing) to detect small-fiber impairment.

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