Why researchers are turning to lithium

• There are about 32 million folks globally residing with Alzheimer’s illness, with that quantity anticipated to hit 152 million by 2050.
• Whereas there are some medicines for Alzheimer’s illness, they’re solely used within the earliest levels to assist sluggish cognitive decline or at extra superior levels to deal with frequent illness signs.
• A new research makes the case for treating Alzheimer’s illness with low-dose lithium because the drug helps to counter neuroprogression and gives neuroprotective advantages.

Researchers additionally consider the quantity of individuals worldwide residing with Alzheimer’s illness and associated dementias will hit 152 million by 2050.

There may be at the moment no treatment for Alzheimer’s illness. Whereas there are some medications accessible, they’re solely used within the earliest levels to assist sluggish cognitive decline or at extra advanced stages to deal with frequent signs of the situation.

“Alzheimer’s illness and different dementias are devastating situations for people, households, and society at giant,” Husseini K Manji, MD, FRCPC, professor at each Oxford College in the UK and at Yale College in the US, co-chair of the U.Okay. Authorities Psychological Well being Objectives Program (previously MH Mission), informed Medical Information In the present day.

“Regardless of latest advances in monoclonal antibodies, Alzheimer’s illness and different dementias stay a large and rising international public well being disaster. Present therapies largely concentrate on single pathologies, reminiscent of eradicating amyloid plaques, however Alzheimer’s is extremely advanced and includes a progressive cascade of mobile vulnerabilities, together with mitochondrial decay, oxidative stress, and lack of synaptic connections,” Manji defined.

He’s the lead writer of a brand new research printed within the journal JAMA Psychiatry making the case for treating Alzheimer’s illness with low-dose lithium — a medicine used to deal with bipolar disorder — because the drug helps to counter neuroprogression and gives neuroprotective advantages.

During the last 25 years, Manji defined, a convergence of molecular, imaging, and epidemiological information from research conducted in his lab and others, has proven that lithium is far more than only a psychiatric drug — it possesses main neurotrophic and neuroprotective properties.

“Nonetheless, conventional psychiatric doses of lithium carbonate are sometimes poorly tolerated by older people attributable to a high adverse effect burden, significantly dangers to kidney and thyroid operate,” he continued.

“My lab, subsequently, did various research with low-dose lithium to point out that lots of the neurotrophic and neuroprotective properties are seen at significantly decrease doses/ranges than these historically utilized in bipolar dysfunction,” Manji informed us.

“These findings have been replicated by different unbiased laboratories,” he famous. “Thus, low-dose lithium might exert neurotrophic results however have significantly fewer unintended effects.”

On this research, Manji and his staff clarify that low-dose lithium is just not solely a temper stabilizer, but in addition helps to counter mind modifications generally known as neuroprogression.

“In bipolar dysfunction, neuroprogression refers back to the method repeated temper episodes trigger cumulative, structural harm, and shrinkage in key mind areas over time,” he detailed.

“Lithium is exclusive as a result of it could actually truly protect and even reverse this mind shrinkage. We consider low-dose lithium can counter an identical progressive decline in Alzheimer’s illness. Lithium exerts results on main neurotrophic cascades — particularly BDNF, bcl-2, and GSK-3 — which might be postulated to attenuate illness development; these findings have been replicated quite a few occasions by unbiased labs.”

– Husseini Okay Manji, MD, FRCPC

“Moreover, in people, lithium remedy has been proven to reverse illness-related neurotrophic deficits in bipolar dysfunction,” Manji added. “Though the ailments are distinct, lithium impacts very basic mobile neurotrophic processes, which might be relevant to Alzheimer’s illness as nicely.”

The research additionally experiences that low-dose lithium might present neuroprotective advantages.

Manji defined that somewhat than simply attempting to wash up a single poisonous protein, low-dose lithium acts like a grasp swap that upgrades the mind’s total mobile protection system by turning up the manufacturing of BDNF, blocking the exercise of deleterious enzymes, and bettering mind energetics.

In brief, he stated, lithium helps susceptible mind cells survive and keep wholesome regardless of the poisonous atmosphere of Alzheimer’s.

“Seventy-five years after remodeling psychiatric care, lithium is on the forefront of a brand new frontier as a robust, multi-targeted intervention able to slowing development in early dementia,” Manji added.

“By shifting our focus to low-dose methods, we are able to harness its sturdy neuroprotective capabilities safely, opening the door to an accessible, low-cost weapon within the international struggle towards Alzheimer’s illness,” he informed us.

MNT had the chance to talk with Laura Nisenbaum, PhD, govt director of drug growth for the Alzheimer’s Drug Discovery Basis (ADDF) — who was not concerned on this analysis — about this research.

Nisenbaum stated her first response to the research was one in every of real curiosity, and what makes this assessment compelling is that so many unbiased strains of proof are pointing in the identical course.

“The sphere has been asking questions on lithium for years, and this assessment synthesizes greater than 2 many years of analysis and presents a case for additional exploration of lithium to find out if it’s a possible disease-modifying remedy, somewhat than merely a repurposed psychiatric medicine,” she defined.

“The breadth of organic rationale can also be intriguing. Lithium seems to behave on a number of organic processes central to Alzheimer’s, together with protein clearance, mitochondrial operate, and tau pathology. That multi-target profile is critical as a result of Alzheimer’s is just not a single-pathway illness,” Nisenbaum detailed.

Nisenbaum harassed it was it is necessary for researchers to proceed to search out new potential remedy choices for Alzheimer’s illness and different kinds of dementia.

“The therapies accessible right this moment supply significant progress, however they depart lots on the desk,” she defined. “There’s a actual alternative to carry new therapies ahead, whether or not together with current therapies or by a precision medication method, the way in which we now deal with most cancers, matching the suitable remedy to the suitable affected person on the proper time.”

“Repurposed medicine like lithium are price taking severely in that context,” Nisenbaum continued. “Lithium has an extended scientific historical past, a well-understood security profile at low doses, and a price and accessibility profile that might make it viable at scale globally.“

“Figuring out established therapies that concentrate on the underlying biology of Alzheimer’s and may realistically attain broad populations is a vital avenue for the sphere to discover,” she stated.

Lastly, MNT additionally spoke to Dung Trinh, MD, internist for the MemorialCare Medical Group and chief medical officer of the Wholesome Mind Clinic in Irvine, CA, about this research.

Trinh, who was not concerned within the analysis, commented that his first response was one in every of cautious optimism.

“This assessment raises an intriguing chance that low-dose lithium might have an effect on a number of organic pathways concerned in neurodegeneration, together with neuronal survival, irritation, oxidative stress, mitochondrial operate, and tau biology,” he, defined.

“That stated, this isn’t but a practice-changing discovering,” he cautioned. “As a clinician, I might not advocate that sufferers begin lithium on their very own, particularly as a result of lithium can have an effect on kidney and thyroid operate and will work together with different medicines.”

“The research is greatest seen as a powerful rationale for rigorous scientific trials, not as proof that lithium must be used routinely for Alzheimer’s prevention or remedy,” Trinh informed us.

“The following step must be a well-designed randomized, placebo-controlled scientific trial in folks with biomarker-confirmed delicate cognitive impairment or early Alzheimer’s illness. Researchers ought to clearly outline the lithium formulation, dose, period, blood-level targets, and safety-monitoring plan, particularly for kidney and thyroid operate. I might additionally prefer to see outcomes that transcend reminiscence testing, together with biomarkers of amyloid, tau, neurodegeneration, MRI changes, every day operate, caregiver-reported outcomes, and high quality of life. The important thing query is whether or not low-dose lithium can present significant mind advantages whereas remaining protected sufficient for older adults over time.”