University of Michigan assistant professor of neurology Dr. Lisa McGinley sheds light on the current developments of stem cell therapies for Alzheimer’s.
With the right signals, non-differentiated human cells called stem cells have the potential to divide and multiply into all different types of cells. Due to this superpower of versatility, scientists are exploring their therapeutic potential to replace damaged cells or tissue. Using stem cells in medical therapies has shown promise as a possible future treatment for neurological conditions like Amyotrophic Lateral Sclerosis (ALS), where stem cell therapies have shown in early studies to protect motor neurons and lengthen the lifespan of mice with the ALS gene, and are currently in stage 3 human clinical trials.
The results have also been a focus of great interest for Alzheimer’s researchers, who are working to crack the code on therapies for a disease that has been notoriously difficult to treat. This group includes University of Michigan Assistant Professor of Neurology Dr. Lisa McGinley. “The great thing about stem cells is that they can provide benefit in multiple ways, compared to drug therapies that typically target a single pathway,” she told Being Patient.
McGinley along with fellow University of Michigan co-investigators Dr. Eva Feldman and Dr. Geoffrey Murphy, is currently testing new therapies for AD in mice models. At the 2021 NIH Alzheimer’s Research Summit last month, McGinley shared encouraging data. “In our studies at the University of Michigan, we have found that transplanting our particular line of neural stem cells improves memory and learning in AD animal models,” she wrote to Being Patient in an email interview leading up to the NIH Summit.
In the long term, McGinley said the team is aiming to achieve similar results in humans, “with the hope of slowing or even stopping memory loss in these patients,” she said.
According to current research by the team, mice who received the stem cell therapies outperformed controls in learning curves and also demonstrated increased retention of learning. One group of mice had genes known as APP and PS1, which are both identified as causative genes for Alzheimer’s and heavily linked with early-onset Alzheimer’s. In addition to performing better, the group of APP/PS1 mice were also found to have reduced beta-amyloid plaque load – a known pathological feature of Alzheimer’s.
“Stem cells can work in several ways to improve brain function,” McGinley explained. “They can differentiate into neurons and they can form contacts with host neurons. They can also produce therapeutic factors and in this way reduce inflammation and provide support to existing cell populations in the brain. We are working hard to understand which of these actions are occurring and which have the greatest impact.”
In a human trial, stem cell treatments would be injected into the brain using MRI guidance. Although this may sound invasive, according to McGinley, there is a broad consensus that intra-cranial injections into the brain are safe, and accordingly, she said they are routinely used in various neurosurgical procedures. She added that the research team is collaborating with neurosurgeons at the University of Michigan in order to ensure the safety of these procedures.
While the results from animal models are promising, McGinley said there is still have some work to do to meet all the requirements necessary to obtain FDA approval for a clinical trial.” , “We are currently completing additional studies in animal models to help us understand how to effectively utilize stem cells in the brain, for instance what dose to use and when is the best time to administer the treatment,” she said.
As such, McGinley said that the time until these therapies become available on the mainstream market will still be a “number of years.”
Investigation continues into the safety and efficacy of these drugs in animal trials, using a variety of doses before testing can be done in human subjects.
In terms of roadblocks, other than funding, facilitating immunosuppression, which involves suppressing a recipients’ immune response to prevent rejection of the stem cells— is another challenge McGinley noted “but, we are learning from the world of organ transplants and developing new ways to prevent rejection of stem cell transplants, while minimizing side effects of immunosuppressive medications.”
Profesa msaidizi wa Chuo Kikuu cha Michigan wa neurolojia Daktari Lisa McGinley anaangazia maendeleo ya sasa ya tiba ya seli za shina kwa Alzheimer. Kwa ishara sahihi, chembe za binadamu zisizo tofauti, zinazoitwa chembe za msingi, zina uwezo wa kugawanyika na kuzidisha katika aina zote tofauti za chembe. Kwa sababu ya uwezo huo mkubwa wa kutumiwa kwa njia mbalimbali, wanasayansi wanachunguza uwezo wao wa kutibu magonjwa ili kubadilisha chembe au tishu zilizoharibiwa. Matibabu ya seli za shina katika matibabu ya matibabu yameonyesha ahadi kama matibabu ya baadaye ya hali za neva kama vile ALS (Amyotrophic Lateral Sclerosis), ambapo matibabu ya seli za shina yameonyesha katika masomo ya mapema kulinda neuroni za gari na kupanua maisha ya panya na jeni la ALS. Matokeo hayo pia yamekuwa kipaumbele cha maslahi makubwa kwa watafiti wa Alzheimer, ambao wanafanya kazi ya kuvunja kanuni ya matibabu ya ugonjwa ambao umekuwa mgumu sana kutibu. Kikundi hiki kinatia ndani Profesa Msaidizi wa Neurolojia wa Chuo Kikuu cha Michigan Dakt. Lisa McGinley. "Kitu kizuri kuhusu seli za shina ni kwamba zinaweza kutoa faida kwa njia nyingi, ikilinganishwa na matibabu ya dawa ambayo kwa kawaida huelekeza njia moja", aliiambia Being Patient. McGinley, pamoja na wenzake wa Chuo Kikuu cha Michigan, Eva Feldman na Geoffrey Murphy, wanajaribu matibabu mapya ya AD katika mifano ya panya. Katika mkutano wa utafiti wa NIH Alzheimer's wa 2021 mwezi uliopita, McGinley alishiriki data ya kutia moyo. "Katika masomo yetu katika Chuo Kikuu cha Michigan, tumegundua kwamba kupandikiza mstari wetu maalum wa seli za msingi za neva huboresha kumbukumbu na kujifunza katika mifano ya wanyama wa AD, ""aliandika kuwa mgonjwa katika mahojiano ya barua pepe inayoongoza kwa Mkutano wa NIH." Kwa muda mrefu, McGinley alisema timu hiyo inakusudia kufikia matokeo kama hayo kwa wanadamu, "kwa matumaini ya kupunguza au hata kusimamisha upotezaji wa kumbukumbu kwa wagonjwa hawa", alisema. Kulingana na utafiti wa sasa na timu, panya ambao walipokea matibabu ya seli za shina walifanya vizuri zaidi kuliko udhibiti katika curves za kujifunza na pia walionyesha kuongezeka kwa uhifadhi wa kujifunza. Kikundi kimoja cha panya kilikuwa na jeni inayojulikana kama APP na PS1, ambazo zote mbili zimetambuliwa kama jeni za kusababisha ugonjwa wa Alzheimer na zinaunganishwa sana na mwanzo wa mapema wa ugonjwa wa Alzheimer. Kwa kuongezea kufanya vizuri zaidi, kundi la panya wa APP-PS1 pia liligunduliwa kuwa na mzigo wa beta-amyloid plake uliopunguzwa - kipengele cha ugonjwa unaojulikana wa Alzheimer. "Seli za shina zinaweza kufanya kazi kwa njia kadhaa ili kuboresha utendaji wa ubongo", McGinley alieleza. <unk> Wanaweza kutofautisha katika neuroni na wanaweza kuunda mawasiliano na neuroni mwenyeji. Pia wanaweza kuzalisha mambo ya matibabu na kwa njia hii kupunguza uvimbe na kutoa msaada kwa idadi ya chembe zilizopo katika ubongo. """Tunafanya kazi kwa bidii kuelewa ni ipi kati ya hatua hizi zinazotokea na ambayo ina athari kubwa zaidi,"" alisema, akisema, ""Katika jaribio la binadamu, matibabu ya seli za shina yangewashwa kwenye ubongo kwa kutumia mwongozo wa MRI." Ingawa hii inaweza kuonekana kuwa ya uvamizi, kulingana na McGinley, kuna makubaliano makubwa kwamba sindano za ndani ya fuvu la kichwa kwenye ubongo ni salama, na kwa hivyo, alisema zinatumiwa kwa kawaida katika taratibu mbalimbali za upasuaji wa neva. "Mwanamke huyo alisema: ""Timu ya utafiti inashirikiana na madaktari wa upasuaji wa neva katika Chuo Kikuu cha Michigan ili kuhakikisha usalama wa taratibu hizi." "Wakati matokeo kutoka kwa mifano ya wanyama ni ya kuahidi, McGinley alisema bado kuna kazi ya kufanya ili kukidhi mahitaji yote muhimu kupata idhini ya FDA kwa majaribio ya kliniki, ""Kwa sasa tunakamilisha masomo ya ziada katika mifano ya wanyama ili kutusaidia kuelewa jinsi ya kutumia seli za msingi kwa ufanisi katika ubongo, kwa mfano ni kipimo gani cha kutumia na ni wakati gani bora wa kutoa matibabu." McGinley alisema kuwa muda wa matibabu hayo kufikia soko kuu bado ni miaka kadhaa, na uchunguzi unaendelea kuhusu usalama na ufanisi wa dawa hizo katika majaribio ya wanyama, kwa kutumia vipimo mbalimbali kabla ya majaribio ya binadamu kufanyika. "Kutokana na changamoto za kuzuia, mbali na ufadhili, kuwezesha immunosuppression, ambayo inajumuisha kukandamiza majibu ya kinga ya wapokeaji ili kuzuia kukataliwa kwa seli za msingi, McGinley alisema, ""lakini, tunajifunza kutoka kwa ulimwengu wa kupandikiza viungo na kuendeleza njia mpya za kuzuia kukataliwa kwa kupandikiza seli za msingi, wakati wa kupunguza athari za dawa za kinga."""