Tim and Matt are preparing to tackle a gruelling 421 kilometre run over 12 days, from Melbourne to Hopetoun, to raise awareness of and funds for Motor Neurone Disease.

The duo have swapped their leather for lycra and on Tuesday, commenced their run from Melbourne to the Mallee. Their reason is simple, to honour their family members who lost their battle with the disease.

Their epic journey will include a stop in Ararat tomorrow and then Stawell on Sunday. Both stops will include a community barbecue.

Averaging 35 kilometres each day, they will arrive in Hopetoun on April 19 and host a concert to celebrate the journey.

"I'm extremely pumped to do this run for Motor Neurone Disease with my mate Matt," Tim Solly said.

"People think we're insane for committing to the gruelling challenge, but all of this is for a good cause."

These daring lads aim to raise awareness and $50,000 for Motor Neurone Disease Victoria, a not for profit organisation which seeks to provide and promote the best possible care and support for people living with MND.

It will be a deeply personal journey in honour of Tim's uncle Darren and Matt's grandfather Tony, who both lost their battle with the disease, which has no known cause, active treatment, remission or cure.

"We're going to face physical exhaustion, mental fatigue and dehydration, not to mention chaffing in the groin area," Tim said.

"We've been training hard, eating well and we've even ditched the beers for green juice. Now we're asking the community to help."

Fundraising Manager at Motor Neurone Disease Victoria, Kathy Nightingale, said her organisation was thrilled with the support from Tim and Matt.

"No matter which way you attack it, running 35 kilometres a day in the rural Australian sun is a tough ask on the lads, who are conditioned to sleeping all day and playing guitar all night," Ms Nightingale said.

"I would like to thank Tim and Matt for what they are going to do, as it will take a lot of commitment, effort and resources on their behalf. We will certainly look to do all we can to promote and help."

When Tim and Matt conquer their journey, there will be a celebration in Hopetoun with live music performances from Dixie Beat, Chooka Williams, Mary Cummins and Dirtland.

There will be a barbecue during the stopover in Ararat and when the boys arrive in Stawell, they will meet with community members during a barbecue and gathering at Cato Park between 4.30pm and 6.30pm. From Stawell, Tim and Matt will head to Dadswells Bridge and then onto Horsham.

All proceeds raised will support MND Victoria.