Top 5 advances in medicine this week

A treatment for a fatal disease; a tissue-integrated bionic knee; explaining why exercise is anti-cancer; a new approach to tackle Alzheimer's; and a virus linked to Parkinson's.

1. Bone marrow transplant treats a fatal disease

ALSP is a rare genetic condition – it stands for Adult-onset Leukoencephalopathy with axonal Spheroids and Pigmented glia. Diagnosis has historically been tricky, but it’s thought that about 0.5-1.5 in 100,000 people are affected – about 10,000 in the US.

The average age at diagnosis is 43, and – once symptoms start – life expectancy is about 8 years. It’s a neurological condition that affects the white matter in the brain (hence ‘leukoencephalopathy’), which leads to cognitive decline and loss of motor function (like walking). There is no cure.

The key to the condition is a lack of functioning microglia - the brain’s macrophages. This is due to mutations in the CSF1R gene (a tyrosine kinase that microglia need to survive and divide). It’s inherited in a dominant manner – so one mutant copy is enough to cause the disease.

The lack of microglia lead to the spheroids (damaged axons that swell and accumulate) and pigmented glia (macrophages from the blood invade the brain and become engorged with myelin breakdown products) in the name.

Microglia normally self-renew, but haematopoietic stem cells – from a bone marrow transplant – can also replace microglia (or microglia-like cells, at least). This is because monocytes (from the transplant) can cross into the brain and form microglia-like cells. This works because the chemotherapy used before a bone-marrow transplant loosens the blood-brain barrier and depletes native microglia.

Bone marrow transplant from donors with wildtype CSF1R was tested here – in 8 patients with ALSP – for the first time. This halted disease progression (shown in these brain MRIs), and maintained cognition and the ability to walk:

Bone marrow transplant prevents progressive damage to the brain in ALSP. Specifically, bone marrow transplant stabilised 1) corpus callosum atrophy 2) cortical atrophy and 3) white matter hyperintensities. Source: this week’s Science.

This is not a benign therapy: it requires high dose chemotherapy to deplete the existing bone marrow and make space for the new cells, which means there’s a risk of infection. And the transplant comes from donors, which means there’s a risk of graft vs. host disease (where the newly-produced immune cells – the graft – attack the patient – the host).

This is a breakthrough, though: it’s the first disease-modifying therapy for ALSP. The key innovation was the ALSP mouse model made during the study, which meant bone marrow transplant could be tested in mice first, before humans.

Importantly, this treatment can stop – but not reverse – progression of ALSP. This means that diagnosis needs to be prompt, but at the moment it's often misdiagnosed (as other neurological conditions, like multiple sclerosis or frontotemporal dementia). Faster genetic testing, for the CSF1R mutant, should help with this.

It was published this week in Science.

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2. A tissue-integrated bionic knee

About 25,000–35,000 above-knee amputations happen every year in the US. The main indications for this are trauma and diabetes. At the moment, above-knee prosthetics use a socket which fits around the residual limb, like this:

But these prosthetics do not integrate into the native anatomy, and – if they could –would allow better, more natural limb control.

This breakthrough prosthetic, in this week’s Science, does exactly that – it’s integrated into the native tissue:

Source