What we
are about

Dis­cover the state of the art of research on Alzheimer’s, heart fail­ure and immune dis­eases, and how ISAR Bioscience intends to advance regen­er­at­ive therapies.

What we are about

Dis­cover the state of the art of research on Alzheimer’s, heart fail­ure and immune dis­eases, and how ISAR Bioscience intends to advance regen­er­at­ive therapies.

Back­ground

ISAR Bioscience is a trans­la­tional com­pany devel­op­ing tech­no­lo­gies and new ther­apies for degen­er­at­ive dis­eases. We work closely with pub­lic research insti­tu­tions and com­pan­ies from the bio­tech­no­logy and phar­ma­ceut­ical indus­tries. We aim to build bridges between these insti­tu­tions and thus cre­ate a dir­ect link between basic research and new ther­apies and products. This is what we mean when we speak of “trans­la­tion”.

The dis­eases that we tar­get are all char­ac­ter­ized by a patho­lo­gical loss of organ func­tion – due to age­ing, insuf­fi­cient blood cir­cu­la­tion or a mal­func­tion­ing immune sys­tem. Examples are Alzheimer’s dis­ease and chronic car­diac fail­ure, which often occurs after a sur­viv­ing heart attack.
In these degen­er­at­ive dis­eases the nat­ural abil­ity of the organs to regen­er­ate from their own stem cells is no longer suf­fi­cient. This leads to the loss of cells and finally to the loss of organ function.

Such dis­eases play a major role world­wide. In most soci­et­ies they rep­res­ent the greatest bur­den of dis­ease, they are respons­ible for most hos­pital admis­sions and are the most fre­quent causes of death. If degen­er­at­ive dis­eases can be pushed back, the vis­ion of healthy age­ing comes within reach.

Read more about such dis­eases and the state of research

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Neuro­de­gen­er­at­ive dis­eases and Alzheimer’s disease

Neuro­de­gen­er­a­tion is an age-related pro­gress­ive deteri­or­a­tion of struc­tures and func­tions of the centra nervous sys­tem. Ulti­mately, this leads to cog­nit­ive dis­ab­il­ity and demen­tia. Neuro­de­gen­er­at­ive dis­eases are a major threat to human health and, due to cur­rent demo­graphic trends, also an enorm­ous socio-eco­nomic bur­den. Besides the par­tic­u­larly well-known Alzheimer’s and Parkinson’s dis­eases, there are many other neuro­de­gen­er­at­ive dis­eases. Most of them are not familial. They appar­ently arise from a com­plex inter­ac­tion of genetic and envir­on­mental risk factors.

Alzheimer’s dis­ease is the most com­mon form of demen­tia and affects mil­lions of people world­wide. Early signs include gaps in short-term memory. As the dis­ease pro­gresses, symp­toms become more pro­nounced and memory and learn­ing are more impaired. Even­tu­ally, speech deteri­or­ates and beha­vi­oural changes become noticeable.

The exact cause of Alzheimer’s demen­tia is not yet fully under­stood. Research focuses on two pro­teins: beta-amyl­oid and tau. These pro­teins accu­mu­late in the brain and form amyl­oid plaques out­side the cells, and so-called neur­ofib­ril­lary tangles inside the cells. Both impair the func­tion and con­nectiv­ity of nerve cells, lead­ing to a pro­gress­ive loss of brain func­tion and a gradual shrink­ing of the brain.

Another explan­a­tion of Alzheimer’s dis­ease focuses on the activ­a­tion of the immune sys­tem and on inflam­mat­ory symp­toms in the affected regions of the brain. This so-called neuroin­flam­ma­tion is a com­mon fea­ture of vir­tu­ally all neuro­de­gen­er­at­ive dis­eases. Microglial cells play a key role in this pro­cess. These are cells of the innate immune sys­tem loc­ated in the brain. They are import­ant for brain devel­op­ment, healthy age­ing and the pro­tec­tion of neurons.

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eart attack and chronic heart failure

Car­di­ovas­cu­lar dis­ease is the most com­mon cause of death and hos­pit­al­isa­tion, often as a res­ult of long-term devel­op­ments. Two of the most com­mon and rel­ev­ant prob­lems are myocar­dial infarc­tion and chronic heart fail­ure – where heart fail­ure is often the res­ult of a pre­vi­ous heart attack.

In a heart attack, tech­nic­ally known as a myocar­dial infarc­tion, an inter­rup­tion in the blood sup­ply to cer­tain regions of the heart leads to cell death and – if not treated very quickly – to the death of the heart muscle in these regions. A myocar­dial infarc­tion is usu­ally accom­pan­ied by severe chest pain that can radi­ate to the shoulders, arms, back or neck. But atyp­ical or even silent infarc­tions also occur, prob­ably more often in women. Often, a myocar­dial infarc­tion occurs in the cen­ter or left side of the chest and lasts longer than a few minutes. The event can have very severe acute con­sequences, includ­ing death from rup­ture of the heart muscle, car­diac shock or arrhythmia (irreg­u­lar heart­beats that can lead to car­diac arrest).

A heart attack is treated acutely with vari­ous med­ic­a­tions and car­diac cath­et­erisa­tion as soon as pos­sible to restore blood flow. But even if this is suc­cess­ful, long-term dam­age often remains. Dying muscle cells are replaced by con­nect­ive tis­sue, a pro­cess tech­nic­ally known as remod­el­ling. As a res­ult, the heart muscle loses its elasti­city and strength. This in turn affects the filling of the heart with blood and its ejec­tion into the blood­stream. This is car­diac failure.

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Dis­eases of the immune system

Our immune sys­tem pro­tects us from harm­ful patho­gens such as vir­uses and bac­teria. To do this, it has to dis­tin­guish exactly what belongs to our body and what is for­eign to it. Some­times this dis­tinc­tion does not work and the immune sys­tem reacts either too strongly or too weakly. This con­trib­utes to many diseases.

In autoim­mune dis­eases, the immune sys­tem is over­act­ive; it attacks and dam­ages our body. Many dis­eases are caused by such over­activ­ity of the immune sys­tem, or at least they have an autoim­mune com­pon­ent. Examples are rheum­atic dis­eases, but also dis­eases of the nervous sys­tem – and even chronic heart fail­ure. On the other hand, a weak immune sys­tem favours infec­tions by vir­uses and bac­teria and can lead to a vari­ety of dis­eases. There­fore, all thera­peutic strategies for dis­eases of the immune sys­tem ulti­mately aim at restor­ing its balance.

Read more about our technologies
and how we use them in our research

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Gen­ome editing

The devel­op­ment of gen­ome edit­ing tech­no­lo­gies is one of the most sig­ni­fic­ant innov­a­tions for basic and applied research in bio­medi­cine. The CRISPR/Cas method, which is based on a com­plex defence mech­an­ism of the immune sys­tem of bac­teria, has revo­lu­tion­ized the way and speed of gen­ome engin­eer­ing. The two dis­cover­ers of this sys­tem, Emmanuelle Char­pen­tier and Jen­nifer Doudna, received the Nobel Prize in Chem­istry in 2020.

The abbre­vi­ation CRISPR stands for Clustered Reg­u­larly Inter­spaced Short Pal­in­dromic Repeat. The CRISPR/Cas sys­tem is a two-part sys­tem. It con­sists of a DNA-cut­ting enzyme, the so-called endo­nuc­lease Cas (CRISPR asso­ci­ated), which can be tar­geted by a small RNA molecule to any pos­i­tion in the gen­ome. There, the endo­nuc­lease leads to double-strand breaks in the DNA. These can be used to intro­duce spe­cific gene muta­tions and thus alter the gen­ome very pre­cisely and in many dif­fer­ent ways. In recent years, numer­ous CRIS­PR/Cas-like sys­tems have been dis­covered in nature.
The tech­no­logy holds enorm­ous poten­tial for almost every bio­tech­no­logy sec­tor. Among oth­ers, it enables the gen­er­a­tion of highly accur­ate dis­ease mod­els for novel thera­peut­ics and diagnostics.

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Stem cells and their differentiation

Human induced pluri­po­tent stem cells (hiPSCs) have opened up com­pletely new hori­zons for research into human dis­eases. With their help, mech­an­isms of dis­ease devel­op­ment can be stud­ied and new ther­apies dis­covered. These are cells that have been repro­grammed from dif­fer­en­ti­ated cells (for example from the skin or blood). Sim­ilar to embryonic stem cells, they are able to renew them­selves and give rise to every cell type in the body. These prop­er­ties make hiPSCs a con­tinu­ous source of human cells and use­ful for a wide range of applications.

Pro­gress in the gen­er­a­tion of three-dimen­sion­ally organ­ized tis­sues from hiPSCs, so-called organoids, has led to enorm­ous advances in dis­ease mod­el­ling. In com­bin­a­tion with gen­ome edit­ing, hiPSC-derived cells and organoids rep­res­ent power­ful mod­els of nat­ural tis­sues and organs. They are also suit­able as tools for cell-based ther­apies and for per­son­al­ized drug screen­ing. Intens­ive research is cur­rently under­way to stand­ard­ize such cells and derived models.